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Yang Chai - One of the best experts on this subject based on the ideXlab platform.
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functional significance of Cranial Neural Crest cells during tooth development and regeneration
Neural Crest Cells#R##N#Evolution Development and Disease, 2014Co-Authors: Carolina Parada, Yang ChaiAbstract:Teeth are complex organs that develop through a series of interactions between the dental epithelium and Neural Crest-derived mesenchyme of the early mammalian embryo. Studies of the molecular regulation of tooth patterning and morphogenesis in the last two decades have demonstrated the involvement of major gene families that are used reiteratively during tooth development. Here, we specifically review the developmental mechanisms and molecular basis underlying tooth shape (type of tooth), tooth number, and number of rows, as well as the generation of successional dentitions, with a focus on the contribution of the Cranial Neural Crest-derived mesenchyme. In addition, we discuss the fate of Neural Crest-derived mesenchymal cells during tooth formation and the presence of mesenchymal stem cells in the adult tooth.
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noncanonical transforming growth factor β tgfβ signaling in Cranial Neural Crest cells causes tongue muscle developmental defects
Journal of Biological Chemistry, 2013Co-Authors: Junichi Iwata, Akiko Suzuki, Richard Pelikan, Thachvu Ho, Yang ChaiAbstract:Microglossia is a congenital birth defect in humans and adversely impacts quality of life. In vertebrates, tongue muscle derives from the Cranial mesoderm, whereas tendons and connective tissues in the craniofacial region originate from Cranial Neural Crest (CNC) cells. Loss of transforming growth factor β (TGFβ) type II receptor in CNC cells in mice (Tgfbr2fl/fl;Wnt1-Cre) causes microglossia due to a failure of cell-cell communication between Cranial mesoderm and CNC cells during tongue development. However, it is still unclear how TGFβ signaling in CNC cells regulates the fate of mesoderm-derived myoblasts during tongue development. Here we show that activation of the cytoplasmic and nuclear tyrosine kinase 1 (ABL1) cascade in Tgfbr2fl/fl;Wnt1-Cre mice results in a failure of CNC-derived cell differentiation followed by a disruption of TGFβ-mediated induction of growth factors and reduction of myogenic cell proliferation and differentiation activities. Among the affected growth factors, the addition of fibroblast growth factor 4 (FGF4) and neutralizing antibody for follistatin (FST; an antagonist of bone morphogenetic protein (BMP)) could most efficiently restore cell proliferation, differentiation, and organization of muscle cells in the tongue of Tgfbr2fl/fl;Wnt1-Cre mice. Thus, our data indicate that CNC-derived fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFβ-mediated regulation of FGF and BMP signaling during tongue development.
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tgf β mediated fgf10 signaling in Cranial Neural Crest cells controls development of myogenic progenitor cells through tissue tissue interactions during tongue morphogenesis
Developmental Biology, 2010Co-Authors: Ryoichi Hosokawa, Junichi Iwata, Mark M Urata, Pablo Bringas, Kyoko Oka, Takayoshi Yamaza, Kazuaki Nonaka, Yang ChaiAbstract:Skeletal muscles are formed from two cell lineages, myogenic and fibroblastic. Mesoderm-derived myogenic progenitors form muscle cells whereas fibroblastic cells give rise to the supportive connective tissue of skeletal muscles, such as the tendons and perimysium. It remains unknown how myogenic and fibroblastic cell-cell interactions affect cell fate determination and the organization of skeletal muscle. In the present study, we investigated the functional significance of cell-cell interactions in regulating skeletal muscle development. Our study shows that Cranial Neural Crest (CNC) cells give rise to the fibroblastic cells of the tongue skeletal muscle in mice. Loss of Tgfbr2 in CNC cells (Wnt1-Cre;Tgfbr2flox/flox) results in microglossia with reduced Scleraxis and Fgf10 expression as well as decreased myogenic cell proliferation, reduced cell number and disorganized tongue muscles. Furthermore, TGF-β2 beads induced the expression of Scleraxis in tongue explant cultures. The addition of FGF10 rescued the muscle cell number in Wnt1-Cre;Tgfbr2flox/flox mice. Thus, TGF-β induced FGF10 signaling has a critical function in regulating tissue-tissue interaction during tongue skeletal muscle development.
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transforming growth factor β regulates basal transcriptional regulatory machinery to control cell proliferation and differentiation in Cranial Neural Crest derived osteoprogenitor cells
Journal of Biological Chemistry, 2010Co-Authors: Junichi Iwata, Ryoichi Hosokawa, Pedro A Sanchezlara, Mark M Urata, Harold C Slavkin, Yang ChaiAbstract:Transforming growth factor-β (Tgf-β) signaling is crucial for regulating craniofacial development. Loss of Tgf-β signaling results in defects in Cranial Neural Crest cells (CNCC), but the mechanism by which Tgf-β signaling regulates bone formation in CNCC-derived osteogenic cells remains largely unknown. In this study, we discovered that Tgf-β regulates the basal transcriptional regulatory machinery to control intramembranous bone development. Specifically, basal transcription factor Taf4b is down-regulated in the CNCC-derived intramembranous bone in Tgfbr2fl/fl;Wnt1-Cre mice. Tgf-β specifically induces Taf4b expression. Moreover, small interfering RNA knockdown of Taf4b results in decreased cell proliferation and altered osteogenic differentiation in primary mouse embryonic maxillary mesenchymal cells, as seen in Tgfbr2 mutant cells. In addition, we show that Taf1 is decreased at the osteogenic initiation stage in the maxilla of Tgfbr2 mutant mice. Furthermore, small interfering RNA knockdown of Taf4b and Taf1 together in primary mouse embryonic maxillary mesenchymal cells results in up-regulated osteogenic initiator Runx2 expression, with decreased cell proliferation and altered osteogenic differentiation. Our results indicate a critical function of Tgf-β-mediated basal transcriptional factors in regulating osteogenic cell proliferation and differentiation in CNCC-derived osteoprogenitor cells during intramembranous bone formation.
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stem cell property of postmigratory Cranial Neural Crest cells and their utility in alveolar bone regeneration and tooth development
Stem Cells, 2009Co-Authors: Hu Zhao, Takayoshi Yamaza, Il Hyuk Chung, Pill Hoon Choung, Songtao Shi, Yang ChaiAbstract:The vertebrate Neural Crest is a multipotent cell population that gives rise to a variety of different cell types. We have discovered that postmigratory Cranial Neural Crest cells (CNCCs) maintain mesenchymal stem cell characteristics and show potential utility for the regeneration of craniofacial structures. We are able to induce the osteogenic differentiation of postmigratory CNCCs, and this differentiation is regulated by bone morphogenetic protein (BMP) and transforming growth factor-β signaling pathways. After transplantation into a host animal, postmigratory CNCCs form bone matrix. CNCC-formed bones are distinct from bones regenerated by bone marrow mesenchymal stem cells. In addition, CNCCs support tooth germ survival via BMP signaling in our CNCC-tooth germ cotransplantation system. Thus, we conclude that postmigratory CNCCs preserve stem cell features, contribute to craniofacial bone formation, and play a fundamental role in supporting tooth organ development. These findings reveal a novel function for postmigratory CNCCs in organ development, and demonstrate the utility of these CNCCs in regenerating craniofacial structures.
Lennart Olsson - One of the best experts on this subject based on the ideXlab platform.
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JOURNAL OF MORPHOLOGY 229:105-120 (1996) Cranial Neural-Crest Migration and Chondrogenic Fate in the Oriental Fire-Bellied Toad Bombina orientalis: Defining the Ancestral Pattern of Head Development in Anuran Amphibians
2013Co-Authors: Lennart Olsson, James HankenAbstract:ABSTRACT We assess Cranial Neural-Crest cell migration and contributions to the larval chondrocranium in the phylogenetically basal and morphologically generalized anuran Bombina orientalis (Bombinatoridae). Methods used include microdissection, scanning electron microscopy, and vital dye labeling, in conjunction with confocal and fluorescence microscopy. Cranial Neural-Crest cells begin migrating before Neural-fold closure and soon form three primary streams. These streams contribute to all Cranial cartilages except two medial components of the hyobranchial skeleton (basihyal and basibranchial cartilages), the posterior portion of the trabecular plate, and the otic capsule, the embryonic origin of which is unknown. Chondrogenic fate is regionalized within the Cranial Neural folds, with the anterior regions contributing to anterior cartilages and the posterior regions to posterior cartilages. A NeuralCrest contribution also was consistently observed in several Cranial nerves and the connective tissue component of many Cranial muscles. Notwithstanding minor differences among species in the initial configuration of migrator
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role of Cranial Neural Crest cells in visceral arch muscle positioning and morphogenesis in the mexican axolotl ambystoma mexicanum
Developmental Dynamics, 2004Co-Authors: Rolf Ericsson, Robert Cerny, Pierre Falck, Lennart OlssonAbstract:The role of Cranial Neural Crest cells in the formation of visceral arch musculature was investigated in the Mexican axolotl, Ambystoma mexicanum. DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine, perchlorate) labeling and green fluorescent protein (GFP) mRNA injections combined with unilateral transplantations of Neural folds showed that Neural Crest cells contribute to the connective tissues but not the myofibers of developing visceral arch muscles in the mandibular, hyoid, and branchial arches. Extirpations of individual Cranial Neural Crest streams demonstrated that Neural Crest cells are necessary for correct morphogenesis of visceral arch muscles. These do, however, initially develop in their proper positions also in the absence of Cranial Neural Crest. Visceral arch muscles forming in the absence of Neural Crest cells start to differentiate at their origins but fail to extend toward their insertions and may have a frayed appearance. Our data indicate that visceral arch muscle positioning is controlled by factors that do not have a Neural Crest origin. We suggest that the Cranial Neural Crest-derived connective tissues provide directional guidance important for the proper extension of the Cranial muscles and the subsequent attachment to the insertion on the correct cartilage. In a comparative context, our data from the Mexican axolotl support the view that the Cranial Neural Crest plays a fundamental role in the development of not only the skeleton of the vertebrate head but also in the morphogenesis of the Cranial muscles and that this might be a primitive feature of Cranial development in vertebrates. Developmental Dynamics 231:237–247, 2004 © 2004 Wiley-Liss, Inc.
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Cranial Neural Crest cell migration in the direct developing frog eleutherodactylus coqui molecular heterogeneity within and among migratory streams
Zoology, 2002Co-Authors: Lennart Olsson, Timothy F. Carl, David J Moury, Olle HastadAbstract:Summary Direct development is a specialized reproductive mode that has evolved repeatedly in many different lineages of amphibians, especially anurans. A fully formed, albeit miniature adult hatches directly from the egg; there is no free-living larva. In many groups, the evolution of direct development has had profound consequences for Cranial development and morphology, including many components that are derived from the embryonic Neural Crest. Yet, the developmental bases of these effects remain poorly known. In order to more fully characterize these changes, we used three molecular markers to analyze Cranial Neural Crest-cell emergence and migration in the direct-developing frog, Eleutherodactylus coqui: HNK-1 immunoreactivity, Dlx protein expression, and cholinesterase activity. Our study validates and extends earlier results showing that the comprehensive changes in embryonic Cranial patterning, differentiation, and developmental timing that are associated with direct development in Eleutherodactylus have not affected gross features of Cranial Neural Crest biology: the relative timing of Crest emergence and the number, configuration and identity of the principal migratory streams closely resemble those seen in metamorphic anurans. The three markers are variably expressed within and among Neural Crest-cell populations. This variation suggests that determination of Cranial Neural Crest-cells may already have begun at or soon after the onset of migration, when the cells emerge from the Neural tube. It is not known how or even if this variation correlates with differential cell lineage or fate. Finally, although HNK-1 expression is widely used to study Neural Crest migration in teleost fishes and amniotes, E. coqui is the only amphibian known in which it effectively labels migrating Neural Crest-cells. There are not enough comparative data to determine whether this feature is functionally associated with direct development or is instead unrelated to reproductive mode.
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Cranial Neural Crest emergence and migration in the mexican axolotl ambystoma mexicanum
Zoology, 2002Co-Authors: Pierre Falck, James Hanken, Lennart OlssonAbstract:Summary The timing and pattern of Cranial Neural Crest cell emergence and migration in the Mexican axolotl, Ambystoma mexicanum, are assessed using scanning electron microscopy (SEM). Cranial Neural Crest cells emerge and begin to migrate at the time of Neural fold closure and soon form three distinct streams. The most anterior (mandibular) stream emerges first, at the level of the mesencephalon. Cells in this stream migrate rostroventrally around the optic vesicle. The second (hyoid) and third (branchial) streams emerge in close succession at the level of the rhombencephalon and extend ventrolaterally. Cells forming the hyoid stream migrate rostral to the otic vesicle, whereas the branchial stream divides into two parallel streams, which migrate caudal to the otic vesicle. At later stages (stage 26 onwards) the Cranial Neural Crest cells disperse into the adjacent mesoderm and can no longer be followed by dissection and SEM. The pattern of Cranial Neural Crest emergence and migration, and division into migratory streams is similar to that in other amphibians and in the Australian lungfish ( Neoceratodus forsteri). Emergence of Crest cells from the Neural tube, relative to the time of Neural tube closure, occurs relatively late in comparison to anurans, but much earlier than in the Australian lungfish. These results establish a morphological foundation for studies in progress on the further development and fate of Cranial Neural Crest cells in the Mexican axolotl, as well as for studies of the role of Cranial Neural Crest in Cranial patterning.
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Cranial Neural Crest Cells Contribute to Connective Tissue in Cranial Muscles in the Anuran Amphibian, Bombina orientalis
Developmental biology, 2001Co-Authors: Lennart Olsson, Kristin H. Lopez, Pierre Falck, Jared Cobb, James HankenAbstract:Abstract The contribution of Cranial Neural Crest cells to the development and patterning of Cranial muscles in amphibians was investigated in the phylogenetically basal and morphologically generalized frog, Bombina orientalis. Experimental methods included fluorescent marking of premigratory Cranial Neural Crest and extirpation of individual migratory streams. Neural Crest cells contributed to the connective tissue component, but not the myofibers, of many larval muscles within the first two branchial arches (mandibular and hyoid), and complex changes in muscle patterning followed Neural Crest extirpation. Connective tissue components of individual muscles of either arch originate from the particular Crest migratory stream that is associated with that arch, and this relationship is maintained regardless of the segmental identity—or embryonic derivation—of associated skeletal components. These developmental relations define a pattern of segmentation in the head of larval anurans that is similar to that previously described in the domestic chicken, the only vertebrate that has been thoroughly investigated in this respect. The fundamental role of the Neural Crest in patterning skeleton and musculature may represent a primitive feature of Cranial development in vertebrates. Moreover, the corresponding developmental processes and cell fates appear to be conserved even when major evolutionary innovations—such as the novel cartilages and muscles of anuran larvae—result in major differences in Cranial form.
James Hanken - One of the best experts on this subject based on the ideXlab platform.
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JOURNAL OF MORPHOLOGY 229:105-120 (1996) Cranial Neural-Crest Migration and Chondrogenic Fate in the Oriental Fire-Bellied Toad Bombina orientalis: Defining the Ancestral Pattern of Head Development in Anuran Amphibians
2013Co-Authors: Lennart Olsson, James HankenAbstract:ABSTRACT We assess Cranial Neural-Crest cell migration and contributions to the larval chondrocranium in the phylogenetically basal and morphologically generalized anuran Bombina orientalis (Bombinatoridae). Methods used include microdissection, scanning electron microscopy, and vital dye labeling, in conjunction with confocal and fluorescence microscopy. Cranial Neural-Crest cells begin migrating before Neural-fold closure and soon form three primary streams. These streams contribute to all Cranial cartilages except two medial components of the hyobranchial skeleton (basihyal and basibranchial cartilages), the posterior portion of the trabecular plate, and the otic capsule, the embryonic origin of which is unknown. Chondrogenic fate is regionalized within the Cranial Neural folds, with the anterior regions contributing to anterior cartilages and the posterior regions to posterior cartilages. A NeuralCrest contribution also was consistently observed in several Cranial nerves and the connective tissue component of many Cranial muscles. Notwithstanding minor differences among species in the initial configuration of migrator
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Cranial Neural Crest emergence and migration in the mexican axolotl ambystoma mexicanum
Zoology, 2002Co-Authors: Pierre Falck, James Hanken, Lennart OlssonAbstract:Summary The timing and pattern of Cranial Neural Crest cell emergence and migration in the Mexican axolotl, Ambystoma mexicanum, are assessed using scanning electron microscopy (SEM). Cranial Neural Crest cells emerge and begin to migrate at the time of Neural fold closure and soon form three distinct streams. The most anterior (mandibular) stream emerges first, at the level of the mesencephalon. Cells in this stream migrate rostroventrally around the optic vesicle. The second (hyoid) and third (branchial) streams emerge in close succession at the level of the rhombencephalon and extend ventrolaterally. Cells forming the hyoid stream migrate rostral to the otic vesicle, whereas the branchial stream divides into two parallel streams, which migrate caudal to the otic vesicle. At later stages (stage 26 onwards) the Cranial Neural Crest cells disperse into the adjacent mesoderm and can no longer be followed by dissection and SEM. The pattern of Cranial Neural Crest emergence and migration, and division into migratory streams is similar to that in other amphibians and in the Australian lungfish ( Neoceratodus forsteri). Emergence of Crest cells from the Neural tube, relative to the time of Neural tube closure, occurs relatively late in comparison to anurans, but much earlier than in the Australian lungfish. These results establish a morphological foundation for studies in progress on the further development and fate of Cranial Neural Crest cells in the Mexican axolotl, as well as for studies of the role of Cranial Neural Crest in Cranial patterning.
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Cranial Neural Crest Cells Contribute to Connective Tissue in Cranial Muscles in the Anuran Amphibian, Bombina orientalis
Developmental biology, 2001Co-Authors: Lennart Olsson, Kristin H. Lopez, Pierre Falck, Jared Cobb, James HankenAbstract:Abstract The contribution of Cranial Neural Crest cells to the development and patterning of Cranial muscles in amphibians was investigated in the phylogenetically basal and morphologically generalized frog, Bombina orientalis. Experimental methods included fluorescent marking of premigratory Cranial Neural Crest and extirpation of individual migratory streams. Neural Crest cells contributed to the connective tissue component, but not the myofibers, of many larval muscles within the first two branchial arches (mandibular and hyoid), and complex changes in muscle patterning followed Neural Crest extirpation. Connective tissue components of individual muscles of either arch originate from the particular Crest migratory stream that is associated with that arch, and this relationship is maintained regardless of the segmental identity—or embryonic derivation—of associated skeletal components. These developmental relations define a pattern of segmentation in the head of larval anurans that is similar to that previously described in the domestic chicken, the only vertebrate that has been thoroughly investigated in this respect. The fundamental role of the Neural Crest in patterning skeleton and musculature may represent a primitive feature of Cranial development in vertebrates. Moreover, the corresponding developmental processes and cell fates appear to be conserved even when major evolutionary innovations—such as the novel cartilages and muscles of anuran larvae—result in major differences in Cranial form.
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Cranial Neural Crest cells contribute to connective tissue in Cranial muscles in the anuran amphibian, Bombina orientalis
2001Co-Authors: Lennart Olsson, Pierre Falck, Jared Cobb, Kristin Lopez, James HankenAbstract:The contribution of Cranial Neural Crest cells to the development and patterning of Cranial muscles in amphibians was investigated in the phylogenetically basal and morphologically generalized frog, Bombina orientalis. Experimental methods included fluorescent marking of premigratory Cranial Neural Crest and extirpation of individual migratory streams. Neural Crest cells contributed to the connective tissue component, but not the myofibers, of many larval muscles within the first two branchial arches (mandibular and hyoid), and complex changes in muscle patterning followed Neural Crest extirpation. Connective tissue components of individual muscles of either arch originate from the particular Crest migratory stream that is associated with that arch, and this relationship is maintained regardless of the segmental identity—or embryonic derivation—of associated skeletal components. These developmental relations define a pattern of segmentation in the head of larval anurans that is similar to that previously described in the domestic chicken, the only vertebrate that has been thoroughly investigated in this respect. The fundamental role of the Neural Crest in patterning skeleton and musculature may represent a primitive feature of Cranial development in vertebrates. Moreover, the corresponding developmental processes and cell fates appear to be conserved even when major evolutionary innovations—such as the novel cartilages and muscles of anuran larvae—result in major differences in Cranial form. © 2001 Academic Press Key Words: Neural Crest; cell migration; cell fate; Bombina; extirpation; vital dye labeling; Cranial muscles
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Cranial Neural Crest migration and chondrogenic fate in the oriental fire bellied toad bombina orientalis defining the ancestral pattern of head development in anuran amphibians
Journal of Morphology, 1996Co-Authors: Lennart Olsson, James HankenAbstract:We assess Cranial Neural-Crest cell migration and contributions to the larval chondrocranium in the phylogenetically basal and morphologically generalized anuran Bombina orientalis (Bombinatoridae). Methods used include microdissection, scanning electron
Pablo Bringas - One of the best experts on this subject based on the ideXlab platform.
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tgf β mediated fgf10 signaling in Cranial Neural Crest cells controls development of myogenic progenitor cells through tissue tissue interactions during tongue morphogenesis
Developmental Biology, 2010Co-Authors: Ryoichi Hosokawa, Junichi Iwata, Mark M Urata, Pablo Bringas, Kyoko Oka, Takayoshi Yamaza, Kazuaki Nonaka, Yang ChaiAbstract:Skeletal muscles are formed from two cell lineages, myogenic and fibroblastic. Mesoderm-derived myogenic progenitors form muscle cells whereas fibroblastic cells give rise to the supportive connective tissue of skeletal muscles, such as the tendons and perimysium. It remains unknown how myogenic and fibroblastic cell-cell interactions affect cell fate determination and the organization of skeletal muscle. In the present study, we investigated the functional significance of cell-cell interactions in regulating skeletal muscle development. Our study shows that Cranial Neural Crest (CNC) cells give rise to the fibroblastic cells of the tongue skeletal muscle in mice. Loss of Tgfbr2 in CNC cells (Wnt1-Cre;Tgfbr2flox/flox) results in microglossia with reduced Scleraxis and Fgf10 expression as well as decreased myogenic cell proliferation, reduced cell number and disorganized tongue muscles. Furthermore, TGF-β2 beads induced the expression of Scleraxis in tongue explant cultures. The addition of FGF10 rescued the muscle cell number in Wnt1-Cre;Tgfbr2flox/flox mice. Thus, TGF-β induced FGF10 signaling has a critical function in regulating tissue-tissue interaction during tongue skeletal muscle development.
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Concerted action of Msx1 and Msx2 in regulating Cranial Neural Crest cell differentiation during frontal bone development.
Mechanisms of development, 2007Co-Authors: Jun Han, Mamoru Ishii, Pablo Bringas, Richard L Maas, Robert E Maxson, Yang ChaiAbstract:The homeobox genes Msx1 and Msx2 function as transcriptional regulators that control cellular proliferation and differentiation during embryonic development. Mutations in the Msx1 and Msx2 genes in mice disrupt tissue-tissue interactions and cause multiple craniofacial malformations. Although Msx1 and Msx2 are both expressed throughout the entire development of the frontal bone, the frontal bone defect in Msx1 or Msx2 null mutants is rather mild, suggesting the possibility of functional compensation between Msx1 and Msx2 during early frontal bone development. To investigate this hypothesis, we generated Msx1(-/-);Msx2(-/-) mice. These double mutant embryos died at E17 to E18 with no formation of the frontal bone. There was no apparent defect in CNC migration into the presumptive frontal bone primordium, but differentiation of the frontal mesenchyme and establishment of the frontal primordium was defective, indicating that Msx1 and Msx2 genes are specifically required for osteogenesis in the Cranial Neural Crest lineage within the frontal bone primordium. Mechanistically, our data suggest that Msx genes are critical for the expression of Runx2 in the frontonasal subpopulation of Cranial Neural Crest cells and for differentiation of the osteogenic lineage. This early function of the Msx genes is likely independent of the Bmp signaling pathway.
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an in vitro model for characterizing the post migratory Cranial Neural Crest cells of the first branchial arch
Developmental Dynamics, 2006Co-Authors: Hu Zhao, Pablo Bringas, Yang ChaiAbstract:The Cranial Neural Crest (CNC) is a transient cell population that originates at the Crest of the Neural fold and gives rise to multiple cell types during craniofacial development. Traditionally, researchers have used tissue explants, such as the Neural tube, to obtain primary Neural Crest cells for their studies. However, this approach has inevitably resulted in simultaneous isolation of Neural and non-Neural Crest cells as both of these cells migrate away from tissue explants. Using the Wnt1-Cre/R26R mouse model, we have obtained a pure population of Neural Crest cells and established a primary CNC cell culture system in which the cell culture medium best supports the proliferation of E10.5 first branchial arch CNC cells and maintains these cells in their undifferentiated state. Differentiation of CNC cells can be initiated by switching to a differentiation medium. In this model, cultured CNC cells can give rise to neurons, glial cells, osteoblasts, and other cell types, faithfully mimicking the differentiation process of the post-migratory CNC cells in vivo. Taken together, our study shows that the Wnt1-Cre/R26R mouse first branchial arch provides an excellent model for obtaining post-migratory Neural Crest cells free of any mesodermal contaminants. The cultured Neural Crest cells are under sustained proliferative, undifferentiated, or lineage-enhanced conditions, hence, serving as a tool for the investigation of the regulatory mechanism of CNC cell fate determination in normal and abnormal craniofacial development.
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tgfβ mediated fgf signaling is crucial for regulating Cranial Neural Crest cell proliferation during frontal bone development
Development, 2005Co-Authors: Tomoyo Sasaki, Mark M Urata, Harold C Slavkin, Pablo Bringas, Yoshihiro Ito, Stanley Chou, Yang ChaiAbstract:The murine frontal bone derives entirely from the Cranial Neural Crest (CNC) and consists of the calvarial (lateral) aspect that covers the frontal lobe of brain and the orbital aspect that forms the roof of bony orbit. TGFbeta and FGF signaling have important regulatory roles in postnatal calvarial development. Our previous study has demonstrated that conditional inactivation of Tgfbr2 in the Neural Crest results in severe defects in calvarial development, although the cellular and molecular mechanisms by which TGFbeta signaling regulates the fate of CNC cells during frontal bone development remain unknown. Here, we show that TGFbeta IIR is required for proliferation of osteoprogenitor cells in the CNC-derived frontal bone anlagen. FGF acts downstream of TGFbeta signaling in regulating CNC cell proliferation, and exogenous FGF2 rescues the cell proliferation defect in the frontal primordium of Tgfbr2 mutant. Furthermore, the CNC-derived frontal primordium requires TGFbeta IIR to undergo terminal differentiation. However, this requirement is restricted to the developing calvarial aspect of the frontal bone, whereas the orbital aspect forms despite the ablation of Tgfbr2 gene, implying a differential requirement for TGFbeta signaling during the development of various regions of the frontal bone. This study demonstrates the biological significance of TGFbeta-mediated FGF signaling cascade in regulating frontal bone development, suggests that TGFbeta functions as a morphogen in regulating the fate of the CNC-derived osteoblast and provides a model for investigating abnormal craniofacial development.
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conditional inactivation of tgfbr2 in Cranial Neural Crest causes cleft palate and calvaria defects
Development, 2003Co-Authors: Yoshihiro Ito, Jun Han, Pablo Bringas, Jae Yong Yeo, Anna Chytil, Akira Nakajima, Charles F Shuler, Harold L Moses, Yang ChaiAbstract:Cleft palate and skull malformations represent some of the most frequent congenital birth defects in the human population. Previous studies have shown that TGFβ signaling regulates the fate of the medial edge epithelium during palatal fusion and postnatal Cranial suture closure during skull development. It is not understood, however, what the functional significance of TGFβ signaling is in regulating the fate of Cranial Neural Crest (CNC) cells during craniofacial development. We show that mice with Tgfbr2 conditional gene ablation in the CNC have complete cleft secondary palate, calvaria agenesis, and other skull defects with complete phenotype penetrance. Significantly, disruption of the TGFβ signaling does not adversely affect CNC migration. Cleft palate in Tgfbr2 mutant mice results from a cell proliferation defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Our data suggests that TGFβ IIR plays a crucial, cell-autonomous role in regulating the fate of CNC cells during palatogenesis. During skull development, disruption of TGFβ signaling in the CNC severely impairs cell proliferation in the dura mater, consequently resulting in calvaria agenesis. We provide in vivo evidence that TGFβ signaling within the CNC-derived dura mater provides essential inductive instruction for both the CNC- and mesoderm-derived calvarial bone development. This study demonstrates that TGFβ IIR plays an essential role in the development of the CNC and provides a model for the study of abnormal CNC development.
Pierre Falck - One of the best experts on this subject based on the ideXlab platform.
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role of Cranial Neural Crest cells in visceral arch muscle positioning and morphogenesis in the mexican axolotl ambystoma mexicanum
Developmental Dynamics, 2004Co-Authors: Rolf Ericsson, Robert Cerny, Pierre Falck, Lennart OlssonAbstract:The role of Cranial Neural Crest cells in the formation of visceral arch musculature was investigated in the Mexican axolotl, Ambystoma mexicanum. DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine, perchlorate) labeling and green fluorescent protein (GFP) mRNA injections combined with unilateral transplantations of Neural folds showed that Neural Crest cells contribute to the connective tissues but not the myofibers of developing visceral arch muscles in the mandibular, hyoid, and branchial arches. Extirpations of individual Cranial Neural Crest streams demonstrated that Neural Crest cells are necessary for correct morphogenesis of visceral arch muscles. These do, however, initially develop in their proper positions also in the absence of Cranial Neural Crest. Visceral arch muscles forming in the absence of Neural Crest cells start to differentiate at their origins but fail to extend toward their insertions and may have a frayed appearance. Our data indicate that visceral arch muscle positioning is controlled by factors that do not have a Neural Crest origin. We suggest that the Cranial Neural Crest-derived connective tissues provide directional guidance important for the proper extension of the Cranial muscles and the subsequent attachment to the insertion on the correct cartilage. In a comparative context, our data from the Mexican axolotl support the view that the Cranial Neural Crest plays a fundamental role in the development of not only the skeleton of the vertebrate head but also in the morphogenesis of the Cranial muscles and that this might be a primitive feature of Cranial development in vertebrates. Developmental Dynamics 231:237–247, 2004 © 2004 Wiley-Liss, Inc.
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Cranial Neural Crest emergence and migration in the mexican axolotl ambystoma mexicanum
Zoology, 2002Co-Authors: Pierre Falck, James Hanken, Lennart OlssonAbstract:Summary The timing and pattern of Cranial Neural Crest cell emergence and migration in the Mexican axolotl, Ambystoma mexicanum, are assessed using scanning electron microscopy (SEM). Cranial Neural Crest cells emerge and begin to migrate at the time of Neural fold closure and soon form three distinct streams. The most anterior (mandibular) stream emerges first, at the level of the mesencephalon. Cells in this stream migrate rostroventrally around the optic vesicle. The second (hyoid) and third (branchial) streams emerge in close succession at the level of the rhombencephalon and extend ventrolaterally. Cells forming the hyoid stream migrate rostral to the otic vesicle, whereas the branchial stream divides into two parallel streams, which migrate caudal to the otic vesicle. At later stages (stage 26 onwards) the Cranial Neural Crest cells disperse into the adjacent mesoderm and can no longer be followed by dissection and SEM. The pattern of Cranial Neural Crest emergence and migration, and division into migratory streams is similar to that in other amphibians and in the Australian lungfish ( Neoceratodus forsteri). Emergence of Crest cells from the Neural tube, relative to the time of Neural tube closure, occurs relatively late in comparison to anurans, but much earlier than in the Australian lungfish. These results establish a morphological foundation for studies in progress on the further development and fate of Cranial Neural Crest cells in the Mexican axolotl, as well as for studies of the role of Cranial Neural Crest in Cranial patterning.
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Cranial Neural Crest Cells Contribute to Connective Tissue in Cranial Muscles in the Anuran Amphibian, Bombina orientalis
Developmental biology, 2001Co-Authors: Lennart Olsson, Kristin H. Lopez, Pierre Falck, Jared Cobb, James HankenAbstract:Abstract The contribution of Cranial Neural Crest cells to the development and patterning of Cranial muscles in amphibians was investigated in the phylogenetically basal and morphologically generalized frog, Bombina orientalis. Experimental methods included fluorescent marking of premigratory Cranial Neural Crest and extirpation of individual migratory streams. Neural Crest cells contributed to the connective tissue component, but not the myofibers, of many larval muscles within the first two branchial arches (mandibular and hyoid), and complex changes in muscle patterning followed Neural Crest extirpation. Connective tissue components of individual muscles of either arch originate from the particular Crest migratory stream that is associated with that arch, and this relationship is maintained regardless of the segmental identity—or embryonic derivation—of associated skeletal components. These developmental relations define a pattern of segmentation in the head of larval anurans that is similar to that previously described in the domestic chicken, the only vertebrate that has been thoroughly investigated in this respect. The fundamental role of the Neural Crest in patterning skeleton and musculature may represent a primitive feature of Cranial development in vertebrates. Moreover, the corresponding developmental processes and cell fates appear to be conserved even when major evolutionary innovations—such as the novel cartilages and muscles of anuran larvae—result in major differences in Cranial form.
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Cranial Neural Crest cells contribute to connective tissue in Cranial muscles in the anuran amphibian, Bombina orientalis
2001Co-Authors: Lennart Olsson, Pierre Falck, Jared Cobb, Kristin Lopez, James HankenAbstract:The contribution of Cranial Neural Crest cells to the development and patterning of Cranial muscles in amphibians was investigated in the phylogenetically basal and morphologically generalized frog, Bombina orientalis. Experimental methods included fluorescent marking of premigratory Cranial Neural Crest and extirpation of individual migratory streams. Neural Crest cells contributed to the connective tissue component, but not the myofibers, of many larval muscles within the first two branchial arches (mandibular and hyoid), and complex changes in muscle patterning followed Neural Crest extirpation. Connective tissue components of individual muscles of either arch originate from the particular Crest migratory stream that is associated with that arch, and this relationship is maintained regardless of the segmental identity—or embryonic derivation—of associated skeletal components. These developmental relations define a pattern of segmentation in the head of larval anurans that is similar to that previously described in the domestic chicken, the only vertebrate that has been thoroughly investigated in this respect. The fundamental role of the Neural Crest in patterning skeleton and musculature may represent a primitive feature of Cranial development in vertebrates. Moreover, the corresponding developmental processes and cell fates appear to be conserved even when major evolutionary innovations—such as the novel cartilages and muscles of anuran larvae—result in major differences in Cranial form. © 2001 Academic Press Key Words: Neural Crest; cell migration; cell fate; Bombina; extirpation; vital dye labeling; Cranial muscles