The Experts below are selected from a list of 5373 Experts worldwide ranked by ideXlab platform
Kathleen J Millen - One of the best experts on this subject based on the ideXlab platform.
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Roof Plate derived radial glial like cells support developmental growth of rapidly adapting mechanoreceptor ascending axons
Cell Reports, 2018Co-Authors: Kim Kridsada, Parthiv Haldipur, Long Ding, Jian J Li, Anne Lindgren, Eloisa Herrera, Victor V Chizhikov, Gareth M. Thomas, Zhiping Wang, Kathleen J MillenAbstract:Summary Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of Roof Plate-derived radial glial-like cells (RGLCs) in the spinal cord dorsal column, which form a network of processes enriched with growth-promoting factors. In dreher mutant mice that lack RGLCs, the lengths of ascending RA mechanoreceptor axon branches are specifically reduced, whereas their descending and collateral branches, and other dorsal column and sensory pathways, are largely unaffected. Because the number and intrinsic growth ability of RA mechanoreceptors are normal in dreher mice, our data suggest that RGLCs provide critical non-cell autonomous growth support for the ascending axons of RA mechanoreceptors. Together, our work identifies a developmental mechanism specifically required for long-range spinal cord longitudinal axons.
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Purkinje cell compartmentalization in the cerebellum of the spontaneous mutant mouse dreher
Brain Structure and Function, 2014Co-Authors: Roy V. Sillitoe, Kathleen J Millen, Nicholas A. George-jones, Richard HawkesAbstract:The cerebellar morphological phenotype of the spontaneous neurological mutant mouse dreher ( Lmx1a ^ dr - J ) results from cell fate changes in dorsal midline patterning involving the Roof Plate and rhombic lip. Positional cloning revealed that the gene Lmx1a , which encodes a LIM homeodomain protein, is mutated in dreher , and is expressed in the developing Roof Plate and rhombic lip. Loss of Lmx1a causes reduction of the Roof Plate, an important embryonic signaling center, and abnormal cell fate specification within the embryonic cerebellar rhombic lip. In adult animals, these defects result in variable, medial fusion of the cerebellar vermis and posterior cerebellar vermis hypoplasia. It is unknown whether deleting Lmx1a results in displacement or loss of specific lobules in the vermis. To distinguish between an ectopic and absent vermis, the expression patterns of two Purkinje cell-specific compartmentation antigens, zebrin II/aldolase C and the small heat shock protein HSP25 were analyzed in dreher cerebella. The data reveal that despite the reduction in volume and abnormal foliation of the cerebellum, the transverse zones and parasagittal stripe arrays characteristic of the normal vermis are present in dreher , but may be highly distorted. In dreher mutants with a severe phenotype, zebrin II stripes are fragmented and distributed non-symmetrically about the cerebellar midline. We conclude that although Purkinje cell agenesis or selective Purkinje cell death may contribute to the dreher phenotype, our data suggest that aberrant anlage patterning and granule cell development lead to Purkinje cell ectopia, which ultimately causes abnormal cerebellar architecture in dreher .
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Overlapping Function of Lmx1a and Lmx1b in Anterior Hindbrain Roof Plate Formation and Cerebellar Growth
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009Co-Authors: Yuriko Mishima, Anne Lindgren, Victor V Chizhikov, Randy L. Johnson, Kathleen J MillenAbstract:The Roof Plate is an organizing center in the dorsal CNS that controls specification and differentiation of adjacent neurons through secretion of the BMP and WNT signaling molecules. Lmx1a, a member of the LIM-homeodomain (LIM-HD) transcription factor family, is expressed in the Roof Plate and its progenitors at all axial levels of the CNS and is necessary and sufficient for Roof Plate formation in the spinal cord. In the anterior CNS, however, a residual Roof Plate develops in the absence of Lmx1a. Lmx1b, another member of the LIM-HD transcription factor family which is highly related to Lmx1a, is expressed in the Roof Plate in the anterior CNS. Although Lmx1b-null mice do not show a substantial deficiency in hindbrain Roof Plate formation, Lmx1a/Lmx1b compound-null mutants fail to generate hindbrain Roof Plate. This observation indicates that both genes act in concert to direct normal hindbrain Roof Plate formation. Since the requirement of Lmx1b function for normal isthmic organizer at the mid-hindbrain boundary complicates analysis of a distinct dorsal patterning role of this gene, we also used a conditional knock-out strategy to specifically delete dorsal midline Lmx1b expression. Phenotypic analysis of single and compound conditional mutants confirmed overlapping roles for Lmx1 genes in regulating hindbrain Roof Plate formation and growth and also revealed roles in regulating adjacent cerebellar morphogenesis. Our data provides the first evidence of overlapping function of the Lmx1 genes during embryonic CNS development.
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Zic1 and Zic4 regulate zebrafish Roof Plate specification and hindbrain ventricle morphogenesis.
Developmental biology, 2007Co-Authors: Gina E. Elsen, Kathleen J Millen, Louis Y. Choi, Yevgenya Grinblat, Victoria E. PrinceAbstract:During development, the lumen of the neural tube develops into a system of brain cavities or ventricles, which play important roles in normal CNS function. We have established that the formation of the hindbrain (4th) ventricle in zebrafish is dependent upon the pleiotropic functions of the genes implicated in human Dandy Walker Malformation, Zic1 and Zic4. Using morpholino knockdown we show that zebrafish Zic1 and Zic4 are required for normal morphogenesis of the 4th ventricle. In Zic1 and/or Zic4 morphants the ventricle does not open properly, but remains completely or partially fused from the level of rhombomere (r) 2 towards the posterior. In the absence of Zic function early hindbrain regionalization and neural crest development remain unaffected, but dorsal hindbrain progenitor cell proliferation is significantly reduced. Importantly, we find that Zic1 and Zic4 are required for development of the dorsal Roof Plate. In Zic morphants expression of Roof Plate markers, including lmx1b.1 and lmx1b.2, is disrupted. We further demonstrate that zebrafish Lmx1b function is required for both hindbrain Roof Plate development and 4th ventricle morphogenesis, confirming that Roof Plate formation is a critical component of ventricle development. Finally, we show that dorsal rhombomere boundary signaling centers depend on Zic1 and Zic4 function and on Roof Plate signals, and provide evidence that these boundary signals are also required for ventricle morphogenesis. In summary, we conclude that Zic1 and Zic4 control zebrafish 4th ventricle morphogenesis by regulating multiple mechanisms including cell proliferation and fate specification in the dorsal hindbrain.
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the Roof Plate regulates cerebellar cell type specification and proliferation
Development, 2006Co-Authors: Victor V Chizhikov, Anne G Lindgren, Spencer D Currle, M Rose, Edwin S Monuki, Kathleen J MillenAbstract:During embryogenesis, the isthmic organizer, a well-described signaling center at the junction of the mid-hindbrain, establishes the cerebellar territory along the anterior/posterior axis of the neural tube. Mechanisms specifying distinct populations within the early cerebellar anlage are less defined. Using a newly developed gene expression map of the early cerebellar anlage, we demonstrate that secreted signals from the rhombomere 1 Roof Plate are both necessary and sufficient for specification of the adjacent cerebellar rhombic lip and its derivative fates. Surprisingly, we show that the Roof Plate is not absolutely required for initial specification of more distal cerebellar cell fates, but rather regulates progenitor proliferation and cell position within the cerebellar anlage. Thus, in addition to the isthmus, the Roof Plate represents an important signaling center controlling multiple aspects of cerebellar patterning.
Victor V Chizhikov - One of the best experts on this subject based on the ideXlab platform.
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Roof Plate derived radial glial like cells support developmental growth of rapidly adapting mechanoreceptor ascending axons
Cell Reports, 2018Co-Authors: Kim Kridsada, Parthiv Haldipur, Long Ding, Jian J Li, Anne Lindgren, Eloisa Herrera, Victor V Chizhikov, Gareth M. Thomas, Zhiping Wang, Kathleen J MillenAbstract:Summary Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of Roof Plate-derived radial glial-like cells (RGLCs) in the spinal cord dorsal column, which form a network of processes enriched with growth-promoting factors. In dreher mutant mice that lack RGLCs, the lengths of ascending RA mechanoreceptor axon branches are specifically reduced, whereas their descending and collateral branches, and other dorsal column and sensory pathways, are largely unaffected. Because the number and intrinsic growth ability of RA mechanoreceptors are normal in dreher mice, our data suggest that RGLCs provide critical non-cell autonomous growth support for the ascending axons of RA mechanoreceptors. Together, our work identifies a developmental mechanism specifically required for long-range spinal cord longitudinal axons.
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Overlapping Function of Lmx1a and Lmx1b in Anterior Hindbrain Roof Plate Formation and Cerebellar Growth
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009Co-Authors: Yuriko Mishima, Anne Lindgren, Victor V Chizhikov, Randy L. Johnson, Kathleen J MillenAbstract:The Roof Plate is an organizing center in the dorsal CNS that controls specification and differentiation of adjacent neurons through secretion of the BMP and WNT signaling molecules. Lmx1a, a member of the LIM-homeodomain (LIM-HD) transcription factor family, is expressed in the Roof Plate and its progenitors at all axial levels of the CNS and is necessary and sufficient for Roof Plate formation in the spinal cord. In the anterior CNS, however, a residual Roof Plate develops in the absence of Lmx1a. Lmx1b, another member of the LIM-HD transcription factor family which is highly related to Lmx1a, is expressed in the Roof Plate in the anterior CNS. Although Lmx1b-null mice do not show a substantial deficiency in hindbrain Roof Plate formation, Lmx1a/Lmx1b compound-null mutants fail to generate hindbrain Roof Plate. This observation indicates that both genes act in concert to direct normal hindbrain Roof Plate formation. Since the requirement of Lmx1b function for normal isthmic organizer at the mid-hindbrain boundary complicates analysis of a distinct dorsal patterning role of this gene, we also used a conditional knock-out strategy to specifically delete dorsal midline Lmx1b expression. Phenotypic analysis of single and compound conditional mutants confirmed overlapping roles for Lmx1 genes in regulating hindbrain Roof Plate formation and growth and also revealed roles in regulating adjacent cerebellar morphogenesis. Our data provides the first evidence of overlapping function of the Lmx1 genes during embryonic CNS development.
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the Roof Plate regulates cerebellar cell type specification and proliferation
Development, 2006Co-Authors: Victor V Chizhikov, Anne G Lindgren, Spencer D Currle, M Rose, Edwin S Monuki, Kathleen J MillenAbstract:During embryogenesis, the isthmic organizer, a well-described signaling center at the junction of the mid-hindbrain, establishes the cerebellar territory along the anterior/posterior axis of the neural tube. Mechanisms specifying distinct populations within the early cerebellar anlage are less defined. Using a newly developed gene expression map of the early cerebellar anlage, we demonstrate that secreted signals from the rhombomere 1 Roof Plate are both necessary and sufficient for specification of the adjacent cerebellar rhombic lip and its derivative fates. Surprisingly, we show that the Roof Plate is not absolutely required for initial specification of more distal cerebellar cell fates, but rather regulates progenitor proliferation and cell position within the cerebellar anlage. Thus, in addition to the isthmus, the Roof Plate represents an important signaling center controlling multiple aspects of cerebellar patterning.
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Roof Plate-dependent patterning of the vertebrate dorsal central nervous system
Developmental biology, 2005Co-Authors: Victor V Chizhikov, Kathleen J MillenAbstract:In the vertebrate central nervous system (CNS), diverse cellular types are generated in response to inductive signals provided by specialized cellular groups that act as organizing centers. The Roof Plate is a critical dorsal signaling center that occupies the dorsal midline of the developing CNS along its entire anterior-posterior axis. During caudal neural tube development, the Roof Plate produces proteins of the Bmp and Wnt families controlling proliferation, specification, migration, and axon guidance of adjacent dorsal interneurons. Although primarily investigated in the developing spinal cord, a growing number of studies indicate that Roof Plate-derived signals are also critical for the patterning of dorsal structures in more rostral regions of CNS including the hindbrain, diencephalon and telencephalon. In this review, we discuss recent progress towards understanding the molecular and cellular mechanisms of Roof Plate-dependent patterning of the dorsal CNS.
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Control of Roof Plate development and signaling by Lmx1b in the caudal vertebrate CNS.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004Co-Authors: Victor V Chizhikov, Kathleen J MillenAbstract:Numerous studies have identified the Roof Plate as an important signaling center controlling dorsal interneuron specification and differentiation in the developing spinal cord. Currently, the molecular pathways of Roof Plate formation and function are poorly understood. We determined that the LIM-homeodomain transcription factor Lmx1b is sufficient to induce functional Roof Plate in the early chick developing spinal cord. In the chick, Lmx1b acts upstream of Lmx1a in the Roof Plate developmental program. Once the Roof Plate forms, we show that Bmp and Wnt signaling are the major components of Lmx1a/b-dependent Roof Plate dorsal patterning activity. The Roof Plate function of Lmx1b is not conserved across vertebrates because Lmx1b is not expressed in mouse Roof Plate progenitors. Instead, mouse caudal CNS Roof Plate formation relies entirely on Lmx1a. Lmx1b can, however, partially rescue Roof Plate development in dreher (Lmx1a-/-) mice, indicating that Lmx1b has some functional redundancy to Lmx1a. Furthermore, we demonstrate that the Roof Plate-inducing activity of Lmx1b can be suppressed by Mash1 (Cash1), which is normally expressed in intermediate neural tube in both chick and mouse. Our data identify Lmx1b as a key regulator of spinal cord Roof Plate induction and function.
Chaya Kalcheim - One of the best experts on this subject based on the ideXlab platform.
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Notch signaling is a critical initiator of Roof Plate formation as revealed by the use of RNA profiling of the dorsal neural tube
2020Co-Authors: Shai Ofek, Sophie Wiszniak, Sarah Kagan, Markus Tondl, Quenten Schwarz, Chaya KalcheimAbstract:The factors underlying establishment of the definitive Roof Plate (RP) and its segregation from neural crest (NC) and interneurons are unknown. We performed transcriptome analysis at trunk levels of quail embryos comparing the dorsal neural tube at premigratory NC and RP stages. This unraveled molecular heterogeneity between NC and RP stages, and within the RP itself. By implementing these genes, we asked whether Notch signaling is involved in RP development. First, we observed that Notch is active at the RP-interneuron interface. Furthermore, gain and loss of Notch function in quail and mouse embryos, respectively, revealed no effect on early NC behavior. Constitutive Notch activation caused a local downregulation of RP markers with a concomitant development of dI1 interneurons, as well as an ectopic upregulation of RP markers in the interneuron domain. Reciprocally, in mice lacking Notch activity both the RP and dI1 interneurons failed to form and this was associated with expansion of the dI2 population. Collectively, our results offer a new resource for defining specific cell types, and provide evidence that Notch is required to establish the definitive RP, and to determine the choice between RP and interneuron fates, but not the segregation of RP from NC. Summary statementA new set of genes involved in Notch-dependent Roof Plate formation is unraveled by transcriptome analysis.
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dynamics of bmp and hes1 hairy1 signaling in the dorsal neural tube underlies the transition from neural crest to definitive Roof Plate
BMC Biology, 2016Co-Authors: Shai Ofek, Erez Nitzan, Oshri Avraham, Nitza Kahane, Deepak Kumar, Chaya KalcheimAbstract:Background The dorsal midline region of the neural tube that results from closure of the neural folds is generally termed the Roof Plate (RP). However, this domain is highly dynamic and complex, and is first transiently inhabited by prospective neural crest (NC) cells that sequentially emigrate from the neuroepithelium. It only later becomes the definitive RP, the dorsal midline cells of the spinal cord. We previously showed that at the trunk level of the axis, prospective RP progenitors originate ventral to the premigratory NC and progressively reach the dorsal midline following NC emigration. However, the molecular mechanisms underlying the end of NC production and formation of the definitive RP remain virtually unknown.
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Dynamics of BMP and Hes1/Hairy1 signaling in the dorsal neural tube underlies the transition from neural crest to definitive Roof Plate.
BMC biology, 2016Co-Authors: Erez Nitzan, Shai Ofek, Oshri Avraham, Nitza Kahane, Deepak Kumar, Chaya KalcheimAbstract:Background The dorsal midline region of the neural tube that results from closure of the neural folds is generally termed the Roof Plate (RP). However, this domain is highly dynamic and complex, and is first transiently inhabited by prospective neural crest (NC) cells that sequentially emigrate from the neuroepithelium. It only later becomes the definitive RP, the dorsal midline cells of the spinal cord. We previously showed that at the trunk level of the axis, prospective RP progenitors originate ventral to the premigratory NC and progressively reach the dorsal midline following NC emigration. However, the molecular mechanisms underlying the end of NC production and formation of the definitive RP remain virtually unknown.
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The dorsal neural tube: a dynamic setting for cell fate decisions.
Developmental neurobiology, 2010Co-Authors: Shlomo Krispin, Erez Nitzan, Chaya KalcheimAbstract:The dorsal neural tube first generates neural crest cells that exit the neural primordium following an epithelial-to-mesenchymal conversion to become sympathetic ganglia, Schwann cells, dorsal root sensory ganglia, and melanocytes of the skin. Following the end of crest emigration, the dorsal midline of the neural tube becomes the Roof Plate, a signaling center for the organization of dorsal neuronal cell types. Recent lineage analysis performed before the onset of crest delamination revealed that the dorsal tube is a highly dynamic region sequentially traversed by fate-restricted crest progenitors. Furthermore, prospective Roof Plate cells were shown to originate ventral to presumptive crest and to progressively relocate dorsalward to occupy their definitive midline position following crest delamination. These data raise important questions regarding the mechanisms of cell emigration in relation to fate acquisition, and suggest the possibility that spatial and/or temporal information in the dorsal neural tube determines initial segregation of neural crest cells into their derivatives. In addition, they emphasize the need to address what controls the end of neural crest production and consequent Roof Plate formation, a fundamental issue for understanding the separation between central and peripheral lineages during development of the nervous system.
Teresa Caprile - One of the best experts on this subject based on the ideXlab platform.
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Complementary expression of EphA7 and SCO-spondin during posterior commissure development
Frontiers in neuroanatomy, 2014Co-Authors: Karen Stanic, Marcela Torrejón, Hernán Montecinos, América Vera, Melissa González, Antonia Recabal, Allison Astuya, Teresa CaprileAbstract:Bilaterally symmetric organisms need to exchange information between the two sides of their bodies in order to integrate sensory inputs and coordinate motor control. This exchange occurs through commissures formed by neurons that project axons across the midline to the contralateral side of the central nervous system. The posterior commissure is the first transversal axonal tract of the embryonic vertebrate brain. It is located in the dorsal portion of the prosomere 1, at the caudal diencephalon. The axons of the posterior commissure principally come from neurons of ventrolateral and dorsolateral pretectal nuclei (parvocellular and magnocellular nucleus of the posterior commissure, respectively) that extend their axons toward the dorsal region. The trajectory of these axons can be divided into the following three stages: 1) dorsal axon extension towards the lateral Roof Plate; 2) fasciculation in the lateral Roof Plate; and 3) midline decision of turning to the ipsilateral side or continuing to the opposite side. The mechanisms and molecules that guide the axons during these steps are unknown. In the present work, immunohistochemical and in situ hybridization analyses were performed, with results suggesting the participation of EphA7 in guiding axons from the ventral to the dorsal region of the prosomere 1 through the generation of an axonal corridor limited by repulsive EphA7 walls. At the lateral Roof Plate, the axons became fasciculated in presence of SCO-spondin until reaching the midline. Finally, EphA7 expression was observed in the diencephalic midline Roof Plate, specifically in the region where some axons turn to the ipsilateral side, suggesting its participation in this decision. In summary, the present work proposes a mechanism of posterior commissure formation orchestrated by the complementary expression of the axon guidance cues SCO-spondin and EphA7.
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Subdivisions of chick diencephalic Roof Plate: Implication in the formation of the posterior commissure
Developmental dynamics : an official publication of the American Association of Anatomists, 2010Co-Authors: Karen Stanic, Hernán Montecinos, Teresa CaprileAbstract:The subcommissural organ (SCO) is a Roof Plate differentiation located in the caudal diencephalon under the posterior commissure (PC). A role for SCO and its secretory product, SCO-spondin, in the formation of the PC has been proposed. Here, we provide immunohistochemical evidence to suggest that SCO is anatomically divided in a bilateral region positive for SCO-spondin that surrounds a negative medial region. Remarkably, axons contacting the lateral region are highly fasciculated, in sharp contrast with the defasciculated axons of the medial region. In addition, lateral axon fascicles run toward the midline inside of tunnels limited by the basal prolongations of SCO cells and extracellular SCO-spondin. Our in vitro data in collagen gel matrices show that SCO-spondin induces axonal growth and fasciculation of pretectal explants. Together, our findings support the idea that SCO-spondin participates in the guidance and fasciculation of axons of the PC. Developmental Dynamics 239:2584–2593, 2010. © 2010 Wiley-Liss, Inc.
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Polarized expression of integrin β1 in diencephalic Roof Plate during chick development, a possible receptor for SCO‐spondin
Developmental dynamics : an official publication of the American Association of Anatomists, 2009Co-Authors: Teresa Caprile, Germán Osorio, Juan Pablo Henríquez, Hernán MontecinosAbstract:The Roof Plate of the caudal diencephalon is formed by the posterior commissure (PC) and the underlying secretory ependyma, the subcommissural organ (SCO). The SCO is composed by radial glial cells bearing processes that cross the PC and attach to the meningeal basement membrane. Since early development, the SCO synthesizes SCO-spondin, a glycoprotein that shares similarities to axonal guidance proteins. In vitro, SCO-spondin promotes neuritic outgrowth through a mechanism mediated by integrin beta1. However, the secretion of SCO-spondin toward the extracellular matrix that surrounds the PC axons and the expression of integrins throughout PC development have not been addressed. Here we provide immunohistochemical evidence to suggest that during chick development SCO cells secrete SCO-spondin through their basal domain, where it is deposited into the extracellular matrix in close contact with axons of the PC that express integrin beta1. Our results suggest that SCO-spondin has a role in the development of the PC through its interaction with integrin beta1.
Shinji Takada - One of the best experts on this subject based on the ideXlab platform.
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Wnt produced by stretched Roof-Plate cells is required for the promotion of cell proliferation around the central canal of the spinal cord
Development (Cambridge England), 2019Co-Authors: Takuma Shinozuka, Ritsuko Takada, Shosei Yoshida, Shigenobu Yonemura, Shinji TakadaAbstract:ABSTRACT Cell morphology changes dynamically during embryogenesis, and these changes create new interactions with surrounding cells, some of which are presumably mediated by intercellular signaling. However, the effects of morphological changes on intercellular signaling remain to be fully elucidated. In this study, we examined the effect of morphological changes in Wnt-producing cells on intercellular signaling in the spinal cord. After mid-gestation, Roof-Plate cells stretched along the dorsoventral axis in the mouse spinal cord, resulting in new contact at their tips with the ependymal cells that surround the central canal. Wnt1 and Wnt3a were produced by the stretched Roof-Plate cells and delivered to the cell process tip. Whereas Wnt signaling was activated in developing ependymal cells, Wnt activation in dorsal ependymal cells, which were close to the stretched Roof Plate, was significantly suppressed in embryos with Roof Plate-specific conditional knockout of Wls , which encodes a factor that is essential for Wnt secretion. Furthermore, proliferation of these cells was impaired in Wls conditional knockout mice during development and after induced spinal cord injury in adults. Therefore, morphological changes in Wnt-producing cells appear to generate new Wnt signal targets.
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r spondin a novel gene with thrombospondin type 1 domain was expressed in the dorsal neural tube and affected in wnts mutants
Biochimica et Biophysica Acta, 2004Co-Authors: Tomoyuki Kamata, Shinji Takada, Kenichi Katsube, Makoto Michikawa, Masahito Yamada, Hidehiro MizusawaAbstract:We identified a novel gene, which encodes a 265-amino-acid sequence with a thrombospondin (TSP) type 1 motif. Unlike the other secretory proteins of the TSP family, this gene encodes no apparent secretion cleavage site, but has a putative nuclear localization signal. Northern blot analysis showed transient expression in the central nervous system (CNS) during development. In situ hybridization showed its expression in the dorsal part of the neural tube on 10 and 12 dpc, especially in the boundary region between Roof Plate and neuroepithelium. This expression was enhanced in the rostral part. The signals were observed in other tissues such as truncal region neighboring forelimbs and mesenchymal tissues around the nasal cavity. We named this gene R-spondin (Roof Plate-specific spondin). Transfection of an epitope-tagged R-spondin into COS7 and 293 cells showed its localization in nuclei and medium, suggesting that R-spondin may become secretory or nuclear protein by some processing, while most of other proteins with TSP type 1 domain are secretory proteins. The expression of R-spondin was reduced in Wnt-1/3a double knockout mouse. R-spondin might be a novel marker of the boundary between the Roof Plate and neuroepithelium and may contribute to the development of dorsal neural tube under the regulation of Wnts.
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Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord
Genes & development, 2002Co-Authors: Yuko Muroyama, Motoyuki Fujihara, Makoto Ikeya, Hisato Kondoh, Shinji TakadaAbstract:In the developing spinal cord, signals from the Roof Plate are required for the development of three classes of dorsal interneuron: D1, D2, and D3, listed from dorsal to ventral. Here, we demonstrate that absence of Wnt1 and Wnt3a, normally expressed in the Roof Plate, leads to diminished development of D1 and D2 neurons and a compensatory increase in D3 neuron populations. This occurs without significantly altered expression of BMP and related genes in the Roof Plate. Moreover, Wnt3a protein induces expression of D1 and D2 markers in the isolated medial region of the chick neural Plate, and Noggin does not interfere with this induction. Thus, Wnt signaling plays a critical role in the specification of cell types for dorsal interneurons.
