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Robb Krumlauf - One of the best experts on this subject based on the ideXlab platform.
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A Hox gene regulatory network for Hindbrain segmentation.
Current topics in developmental biology, 2020Co-Authors: Hugo J. Parker, Robb KrumlaufAbstract:Abstract In vertebrates, the Hindbrain serves as a highly conserved complex coordination center for regulating many fundamental activities of the central nervous system, such as respiratory rhythms, sleep patterns and equilibrium, and it also plays an important role in craniofacial development. The basic ground plan that underlies the diverse functions of the Hindbrain and its neural crest derivatives is established and patterned by a process of segmentation. Through a dynamic series of signaling and regulatory interactions the developing Hindbrain is transiently compartmentalized into a set of seven segmental units, termed rhombomeres. The nested expression of the Hox family of transcription factors is tightly coupled to the process of segmentation and provides a molecular code for specifying the unique regional properties of the Hindbrain and its neural crest derived craniofacial structures. The high degree of similarity in Hindbrain architecture between diverse vertebrates has enabled cross-species regulatory analysis. This has facilitated the experimental assembly of the signaling and regulatory interactions, which underlie the process of segmentation, into a Hox-dependent gene regulatory network (GRN) model. This Hindbrain GRN is a key regulatory feature of head patterning, conserved to the base of vertebrate evolution. This regulatory framework also serves as a basis for comparing and contrasting GRNs that govern cranial neural crest formation and axial patterning and provide insight into regulatory mechanisms associated with the evolution of novel vertebrate traits. The purpose of this review is to discuss the majorfeatures of the GRN for Hindbrain segmentation and its relationship to the broader functional role of the Hindbrain in patterning head development.
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an atlas of anterior hox gene expression in the embryonic sea lamprey head hox code evolution in vertebrates
Developmental Biology, 2019Co-Authors: Hugo J. Parker, Robb Krumlauf, Marianne E. BronnerAbstract:In the Hindbrain and the adjacent cranial neural crest (NC) cells of jawed vertebrates (gnathostomes), nested and segmentally-restricted domains of Hox gene expression provide a combinatorial Hox-code for specifying regional properties during head development. Extant jawless vertebrates, such as the sea lamprey (Petromyzon marinus), can provide insights into the evolution and diversification of this Hox-code in vertebrates. There is evidence for gnathostome-like spatial patterns of Hox expression in lamprey; however, the expression domains of the majority of lamprey hox genes from paralogy groups (PG) 1-4 are yet to be characterized, so it is unknown whether they are coupled to Hindbrain segments (rhombomeres) and NC. In this study, we systematically describe the spatiotemporal expression of all 14 sea lamprey hox genes from PG1-PG4 in the developing Hindbrain and pharynx to investigate the extent to which their expression conforms to the archetypal gnathostome Hindbrain and pharyngeal hox-codes. We find many similarities in Hox expression between lamprey and gnathostome species, particularly in rhombomeric domains during Hindbrain segmentation and in the cranial neural crest, enabling inference of aspects of Hox expression in the ancestral vertebrate embryonic head. These data are consistent with the idea that a Hox regulatory network underlying Hindbrain segmentation is a pan vertebrate trait. We also reveal differences in Hindbrain domains at later stages, as well as expression in the endostyle and in pharyngeal arch (PA) 1 mesoderm. Our analysis suggests that many Hox expression domains that are observed in extant gnathostomes were present in ancestral vertebrates but have been partitioned differently across Hox clusters in gnathostome and cyclostome lineages after duplication.
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The vertebrate Hox gene regulatory network for Hindbrain segmentation: Evolution and diversification
BioEssays : news and reviews in molecular cellular and developmental biology, 2016Co-Authors: Hugo J. Parker, Marianne E. Bronner, Robb KrumlaufAbstract:Hindbrain development is orchestrated by a vertebrate gene regulatory network that generates segmental patterning along the anterior–posterior axis via Hox genes. Here, we review analyses of vertebrate and invertebrate chordate models that inform upon the evolutionary origin and diversification of this network. Evidence from the sea lamprey reveals that the Hindbrain regulatory network generates rhombomeric compartments with segmental Hox expression and an underlying Hox code. We infer that this basal feature was present in ancestral vertebrates and, as an evolutionarily constrained developmental state, is fundamentally important for patterning of the vertebrate Hindbrain across diverse lineages. Despite the common ground plan, vertebrates exhibit neuroanatomical diversity in lineage-specific patterns, with different vertebrates revealing variations of Hox expression in the Hindbrain that could underlie this diversification. Invertebrate chordates lack Hindbrain segmentation but exhibit some conserved aspects of this network, with retinoic acid signaling playing a role in establishing nested domains of Hox expression.
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A Hox regulatory network of Hindbrain segmentation is conserved to the base of vertebrates
Nature, 2014Co-Authors: Hugo J. Parker, Marianne E. Bronner, Robb KrumlaufAbstract:A defining feature governing head patterning of jawed vertebrates is a highly conserved gene regulatory network that integrates Hindbrain segmentation with segmentally restricted domains of Hox gene expression. Although non-vertebrate chordates display nested domains of axial Hox expression, they lack Hindbrain segmentation. The sea lamprey, a jawless fish, can provide unique insights into vertebrate origins owing to its phylogenetic position at the base of the vertebrate tree. It has been suggested that lamprey may represent an intermediate state where nested Hox expression has not been coupled to the process of Hindbrain segmentation. However, little is known about the regulatory network underlying Hox expression in lamprey or its relationship to Hindbrain segmentation. Here, using a novel tool that allows cross-species comparisons of regulatory elements between jawed and jawless vertebrates, we report deep conservation of both upstream regulators and segmental activity of enhancer elements across these distant species. Regulatory regions from diverse gnathostomes drive segmental reporter expression in the lamprey Hindbrain and require the same transcriptional inputs (for example, Kreisler (also known as Mafba), Krox20 (also known as Egr2a)) in both lamprey and zebrafish. We find that lamprey hox genes display dynamic segmentally restricted domains of expression; we also isolated a conserved exonic hox2 enhancer from lamprey that drives segmental expression in rhombomeres 2 and 4. Our results show that coupling of Hox gene expression to segmentation of the Hindbrain is an ancient trait with origin at the base of vertebrates that probably led to the formation of rhombomeric compartments with an underlying Hox code.
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Hox genes and segmentation of the vertebrate Hindbrain.
Current topics in developmental biology, 2009Co-Authors: Stefan Tümpel, Leanne M. Wiedemann, Robb KrumlaufAbstract:In the vertebrate central nervous system, the Hindbrain is an important center for coordinating motor activity, posture, equilibrium, sleep patterns, and essential unconscious functions, such as breathing rhythms and blood circulation. During development, the vertebrate Hindbrain depends upon the process of segmentation or compartmentalization to create and organize regional properties essential for orchestrating its highly conserved functional roles. The process of segmentation in the Hindbrain differs from that which functions in the paraxial mesoderm to generate somites and the axial skeleton. In the prospective Hindbrain, cells in the neural epithelia transiently alter their ability to interact with their neighbors, resulting in the formation of seven lineage-restricted cellular compartments. These different segments or rhombomeres each go on to adopt unique characters in response to environmental signals. The Hox family of transcription factors is coupled to this process. Overlapping or nested patterns of Hox gene expression correlate with segmental domains and provide a combinatorial code and molecular framework for specifying the unique identities of Hindbrain segments. The segmental organization and patterns of Hox expression and function are highly conserved among vertebrates and, as a consequence, comparative studies between different species have greatly enhanced our ability to build a picture of the regulatory cascades that control early Hindbrain development. The purpose of this chapter is to review what is known about the regulatory mechanisms which establish and maintain Hox gene expression and function in Hindbrain development.
Robert Baker - One of the best experts on this subject based on the ideXlab platform.
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Neurovascular development in the embryonic zebrafish Hindbrain
Developmental biology, 2011Co-Authors: Florian Ulrich, Robert Baker, Jesús Torres-vázquezAbstract:The brain is made of billions of highly metabolically active neurons whose activities provide the seat for cognitive, affective, sensory and motor functions. The cerebral vasculature meets the brain's unusually high demand for oxygen and glucose by providing it with the largest blood supply of any organ. Accordingly, disorders of the cerebral vasculature, such as congenital vascular malformations, stroke and tumors, compromise neuronal function and survival and often have crippling or fatal consequences. Yet, the assembly of the cerebral vasculature is a process that remains poorly understood. Here we exploit the physical and optical accessibility of the zebrafish embryo to characterize cerebral vascular development within the embryonic Hindbrain. We find that this process is primarily driven by endothelial cell migration and follows a two-step sequence. First, perineural vessels with stereotypical anatomies are formed along the ventro-lateral surface of the neuroectoderm. Second, angiogenic sprouts derived from a subset of perineural vessels migrate into the Hindbrain to form the intraneural vasculature. We find that these angiogenic sprouts reproducibly penetrate into the Hindbrain via the rhombomere centers, where differentiated neurons reside, and that specific rhombomeres are invariably vascularized first. While the anatomy of intraneural vessels is variable from animal to animal, some aspects of the connectivity of perineural and intraneural vessels occur reproducibly within particular Hindbrain locales. Using a chemical inhibitor of VEGF signaling we determine stage-specific requirements for this pathway in the formation of the Hindbrain vasculature. Finally, we show that a subset of Hindbrain vessels is aligned and/or in very close proximity to stereotypical neuron clusters and axon tracts. Using endothelium-deficient cloche mutants we show that the endothelium is dispensable for the organization and maintenance of these stereotypical neuron clusters and axon tracts in the early Hindbrain. However, the cerebellum's upper rhombic lip and the optic tectum are abnormal in clo. Overall, this study provides a detailed, multi-stage characterization of early zebrafish Hindbrain neurovascular development with cellular resolution up to the third day of age. This work thus serves as a useful reference for the neurovascular characterization of mutants, morphants and drug-treated embryos.
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Ancestry of motor innervation to pectoral fin and forelimb
Nature Communications, 2010Co-Authors: Leung-hang Ma, Edwin Gilland, Andrew H. Bass, Robert BakerAbstract:Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the Hindbrain among ray-finned fish. New and previous data for lobe-finned fish, a group that includes tetrapods, and more basal cartilaginous fish showed pectoral innervation that was consistent with a Hindbrain-spinal origin of motoneurons. Together, these findings support a Hindbrain–spinal phenotype as the ancestral vertebrate condition that originated as a postural adaptation for pectoral control of head orientation. A phylogenetic analysis indicated that Hox gene modules were shared in fish and tetrapod pectoral systems. We propose that evolutionary shifts in Hox gene expression along the body axis provided a transcriptional mechanism allowing eventual decoupling of pectoral motoneurons from the Hindbrain much like their target appendage gained independence from the head.It was previously thought that the nerves in the pectoral fin of fish came solely from the spinal cord. Here, motoneurons in ray-finned fish are shown to also originate from the Hindbrain, demonstrating that innervation was from both the Hindbrain and the spinal cord in ancesteral vertebrates.
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ancestry of motor innervation to pectoral fin and forelimb
Nature Communications, 2010Co-Authors: Edwin Gilland, Andrew H. Bass, Robert BakerAbstract:Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the Hindbrain among ray-finned fish. New and previous data for lobe-finned fish, a group that includes tetrapods, and more basal cartilaginous fish showed pectoral innervation that was consistent with a Hindbrain-spinal origin of motoneurons. Together, these findings support a Hindbrain–spinal phenotype as the ancestral vertebrate condition that originated as a postural adaptation for pectoral control of head orientation. A phylogenetic analysis indicated that Hox gene modules were shared in fish and tetrapod pectoral systems. We propose that evolutionary shifts in Hox gene expression along the body axis provided a transcriptional mechanism allowing eventual decoupling of pectoral motoneurons from the Hindbrain much like their target appendage gained independence from the head.
Charles B. Kimmel - One of the best experts on this subject based on the ideXlab platform.
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FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish Hindbrain.
Development (Cambridge England), 2002Co-Authors: Lisa Maves, William R. Jackman, Charles B. KimmelAbstract:The segmentation of the vertebrate Hindbrain into rhombomeres is highly conserved, but how early Hindbrain patterning is established is not well understood. We show that rhombomere 4 (r4) functions as an early-differentiating signaling center in the zebrafish Hindbrain. Time-lapse analyses of zebrafish Hindbrain development show that r4 forms first and Hindbrain neuronal differentiation occurs first in r4. Two signaling molecules, FGF3 and FGF8, which are both expressed early in r4, are together required for the development of rhombomeres adjacent to r4, particularly r5 and r6. Transplantation of r4 cells can induce expression of r5/r6 markers, as can misexpression of either FGF3 or FGF8. Genetic mosaic analyses also support a role for FGF signaling acting from r4. Taken together, our findings demonstrate a crucial role for FGF-mediated inter-rhombomere signaling in promoting early Hindbrain patterning and underscore the significance of organizing centers in patterning the vertebrate neural plate.
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islet reveals segmentation in the Amphioxus Hindbrain homolog.
Developmental biology, 2000Co-Authors: William R. Jackman, James A. Langeland, Charles B. KimmelAbstract:The vertebrate embryonic Hindbrain is segmented into rhombomeres. Gene expression studies suggest that amphioxus, the closest invertebrate relative of vertebrates, has a Hindbrain homolog. However, this region is not overtly segmented in amphioxus, raising the question of how Hindbrain segmentation arose in chordate evolution. Vertebrate Hindbrain segmentation includes the patterning of cranial motor neurons, which can be identified by their expression of the LIM-homeodomain transcription factor islet1. To learn if the amphioxus Hindbrain homolog is cryptically segmented, we cloned an amphioxus gene closely related to islet1, which we named simply islet. We report that amphioxus islet expression includes a domain of segmentally arranged cells in the ventral Hindbrain homolog. We hypothesize that these cells are developing motor neurons and reveal a form of Hindbrain segmentation in amphioxus. Hence, vertebrate rhombomeres may derive from a cryptically segmented brain present in the amphioxus/vertebrate ancestor. Other islet expression domains provide evidence for amphioxus homologs of the pineal gland, adenohypophysis, and endocrine pancreas. Surprisingly, homologs of vertebrate islet1-expressing spinal motor neurons and Rohon-Beard sensory neurons appear to be absent.
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zebrafish hox genes expression in the Hindbrain region of wild type and mutants of the segmentation gene valentino
Development, 1998Co-Authors: Victoria E Prince, Cecilia B Moens, Charles B. KimmelAbstract:The developing Hindbrain is organized into a series of segments termed rhombomeres which represent lineage restricted compartments correlating with domains of gene expression and neuronal differentiation. In this study, we investigate the processes of Hindbrain segmentation and the acquisition of segmental identity by analyzing the expression of zebrafish hox genes in the Hindbrains of normal fish and fish with a loss-of-function mutation in the segmentation gene valentino (val, the homologue of mouse kreisler; Moens, C. B., Cordes, S. P. Giorgianni, M. W., Barsh, G. S. and Kimmel, C. B. (1998). Development 125, 381–391). We find that zebrafish hox genes generally have similar expression profiles to their murine and avian counterparts, although there are several differences in timing and spatial extent of expression which may underlie some of the functional changes that have occurred along the separate evolutionary lineages of teleosts and tetrapods. Our analysis of hox gene expression in val- embryos confirms that the val gene product is important for subdivision of the presumptive rhombomere 5 and 6 territory into definitive rhombomeres, suggests that the val gene product plays a critical role in regulating hox gene transcription, and indicates that some neural crest cells are inappropriately specified in val- embryos. Our analysis of gene expression at several developmental stages has allowed us to infer differences between primary and secondary defects in the val mutant: we find that extended domains of expression for some hox genes are secondary, late phenomena potentially resulting from inappropriate cell mixing or lack of normal inter-rhombomeric interactions in the caudal Hindbrain.
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Equivalence in the genetic control of Hindbrain segmentation in fish and mouse
Development (Cambridge England), 1998Co-Authors: Cecilia B Moens, Sabine P. Cordes, M.w. Giorgianni, Gregory S. Barsh, Charles B. KimmelAbstract:The vertebrate Hindbrain is subdivided into a series of rhombomeres whose segmental organization serves to pattern the architecture and innervation of the developing head. The zebrafish gene valentino is required cell-autonomously in the development of rhombomeres 5 and 6, and valentino mutants lack visible Hindbrain segmentation caudal to the r3/4 boundary (Moens, C. B., Yan, Y.-L., Appel, B., Force, A. G., and Kimmel, C. B. (1996) Development 122, 3981–3990). Here we show that valentino is the zebrafish homologue of the mouse segmentation gene kreisler, which encodes a bZip transcription factor. The valentino gene is expressed in a manner consistent with its proposed role in subdividing rhombomeres 5 and 6 from their common precursor ‘proto-segment’ in the presumptive Hindbrain, a process that we also demonstrate is reflected in the normal order of appearance of rhombomere boundaries. As well as having similar phenotypes with respect to visible Hindbrain segmentation and patterns of marker gene expression, valentino and kreisler mutants have similar pharyngeal arch and inner ear defects, consistent with a conserved role for this gene in Hindbrain segmentation and in patterning of the head periphery.
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valentino: a zebrafish gene required for normal Hindbrain segmentation.
Development (Cambridge England), 1996Co-Authors: Cecilia B Moens, Yi-lin Yan, Bruce Appel, Allan G. Force, Charles B. KimmelAbstract:Mutational analysis can serve both to identify new genes essential for patterning embryonic development and to determine their functions. Here we describe the identification and phenotypic characterization of alleles of valentino, which we recovered in a genetic screen that sought to identify mutations in the zebrafish that disrupt region-specific gene expression patterns in the embryonic brain. valentino is required for normal Hindbrain segmentation and the Hindbrain of valentino mutant embryos is shortened by the length of one rhombomere. We demonstrate that valentino is required cell-autonomously in the development of rhombomeres 5 and 6, and propose that valentino functions in the subdivision and expansion of a common precursor region in the presumptive Hindbrain into the definitive rhombomeres 5 and 6. These results provide genetic evidence for a two-segment periodicity in the Hindbrain and suggest that this periodicity arises sequentially, through the specification and later subdivision of a two-rhombomere unit, or ‘protosegment’.
Cecilia B Moens - One of the best experts on this subject based on the ideXlab platform.
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cyp26 enzymes generate the retinoic acid response pattern necessary for Hindbrain development
Development, 2007Co-Authors: Rafael E Hernandez, Aaron P Putzke, Jonathan P Myers, Lilyana Margaretha, Cecilia B MoensAbstract:Retinoic acid (RA) is essential for normal vertebrate development, including the patterning of the central nervous system. During early embryogenesis, RA is produced in the trunk mesoderm through the metabolism of vitamin A derived from the maternal diet and behaves as a morphogen in the developing Hindbrain where it specifies nested domains of Hox gene expression. The loss of endogenous sources of RA can be rescued by treatment with a uniform concentration of exogenous RA, indicating that domains of RA responsiveness can be shaped by mechanisms other than the simple diffusion of RA from a localized posterior source. Here, we show that the cytochrome p450 enzymes of the Cyp26 class, which metabolize RA into polar derivatives, function redundantly to shape RA-dependent gene-expression domains during Hindbrain development. In zebrafish embryos depleted of the orthologs of the three mammalian CYP26 genes CYP26A1, CYP26B1 and CYP26C1 , the entire Hindbrain expresses RA-responsive genes that are normally restricted to nested domains in the posterior Hindbrain. Furthermore, we show that Cyp26 enzymes are essential for exogenous RA to rescue Hindbrain patterning in RA-depleted embryos. We present a `gradient-free9 model for Hindbrain patterning in which differential RA responsiveness along the Hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes.
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Constructing the Hindbrain: insights from the zebrafish.
Developmental dynamics : an official publication of the American Association of Anatomists, 2002Co-Authors: Cecilia B Moens, Victoria E PrinceAbstract:The Hindbrain is responsible for controlling essential functions such as respiration and heart beat that we literally do not think about most of the time. In addition, cranial nerves projecting from the Hindbrain control muscles in the jaw, eye, and face, and receive sensory input from these same areas. In all vertebrates that have been studied, the Hindbrain passes through a segmented phase shortly after the neural tube has formed, with a series of seven bulges--the rhombomeres--forming along the anterior-posterior extent of the neural tube. Our current understanding of vertebrate Hindbrain development comes from integrating data from several model systems. Work on the chick has helped us to understand the cell biology of the rhombomeres, whereas the power of mouse molecular genetics has allowed investigation of the molecular mechanisms underlying their development. This review focuses on the special insights that the zebrafish system has provided to our understanding of Hindbrain development. As we will discuss, work in the zebrafish has elucidated inductive events that specify the presumptive Hindbrain domain and has identified genes required for Hindbrain segmentation and the specification of segment identities.
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Eliminating zebrafish pbx proteins reveals a Hindbrain ground state.
Developmental cell, 2002Co-Authors: Andrew J. Waskiewicz, Holly A. Rikhof, Cecilia B MoensAbstract:Abstract The vertebrate Hindbrain is divided into serially homologous segments, the rhombomeres (r). Pbx and Hox proteins are hypothesized to form heterodimeric, DNA binding transcription complexes which specify rhombomere identities. Here, we show that eliminating zebrafish Lzr/Pbx4 and Pbx2 function prevents Hindbrain segmentation and causes a wholesale anterior homeotic transformation of r2–r6, to r1 identity. We demonstrate that Pbx proteins interact with Hox paralog group 1 proteins to specify segment identities broadly within the Hindbrain, and that this process involves the Pbx:Hox-1-dependent induction of Fgf signals in r4. We propose that in the absence of Pbx function, r2–r6 acquire a homogeneous ground state identity, that of r1, and that Pbx proteins, functioning primarily with their Hox partners, function to modify this ground state identity during normal Hindbrain development.
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zebrafish hox genes expression in the Hindbrain region of wild type and mutants of the segmentation gene valentino
Development, 1998Co-Authors: Victoria E Prince, Cecilia B Moens, Charles B. KimmelAbstract:The developing Hindbrain is organized into a series of segments termed rhombomeres which represent lineage restricted compartments correlating with domains of gene expression and neuronal differentiation. In this study, we investigate the processes of Hindbrain segmentation and the acquisition of segmental identity by analyzing the expression of zebrafish hox genes in the Hindbrains of normal fish and fish with a loss-of-function mutation in the segmentation gene valentino (val, the homologue of mouse kreisler; Moens, C. B., Cordes, S. P. Giorgianni, M. W., Barsh, G. S. and Kimmel, C. B. (1998). Development 125, 381–391). We find that zebrafish hox genes generally have similar expression profiles to their murine and avian counterparts, although there are several differences in timing and spatial extent of expression which may underlie some of the functional changes that have occurred along the separate evolutionary lineages of teleosts and tetrapods. Our analysis of hox gene expression in val- embryos confirms that the val gene product is important for subdivision of the presumptive rhombomere 5 and 6 territory into definitive rhombomeres, suggests that the val gene product plays a critical role in regulating hox gene transcription, and indicates that some neural crest cells are inappropriately specified in val- embryos. Our analysis of gene expression at several developmental stages has allowed us to infer differences between primary and secondary defects in the val mutant: we find that extended domains of expression for some hox genes are secondary, late phenomena potentially resulting from inappropriate cell mixing or lack of normal inter-rhombomeric interactions in the caudal Hindbrain.
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Equivalence in the genetic control of Hindbrain segmentation in fish and mouse
Development (Cambridge England), 1998Co-Authors: Cecilia B Moens, Sabine P. Cordes, M.w. Giorgianni, Gregory S. Barsh, Charles B. KimmelAbstract:The vertebrate Hindbrain is subdivided into a series of rhombomeres whose segmental organization serves to pattern the architecture and innervation of the developing head. The zebrafish gene valentino is required cell-autonomously in the development of rhombomeres 5 and 6, and valentino mutants lack visible Hindbrain segmentation caudal to the r3/4 boundary (Moens, C. B., Yan, Y.-L., Appel, B., Force, A. G., and Kimmel, C. B. (1996) Development 122, 3981–3990). Here we show that valentino is the zebrafish homologue of the mouse segmentation gene kreisler, which encodes a bZip transcription factor. The valentino gene is expressed in a manner consistent with its proposed role in subdividing rhombomeres 5 and 6 from their common precursor ‘proto-segment’ in the presumptive Hindbrain, a process that we also demonstrate is reflected in the normal order of appearance of rhombomere boundaries. As well as having similar phenotypes with respect to visible Hindbrain segmentation and patterns of marker gene expression, valentino and kreisler mutants have similar pharyngeal arch and inner ear defects, consistent with a conserved role for this gene in Hindbrain segmentation and in patterning of the head periphery.
Dalit Sela-donenfeld - One of the best experts on this subject based on the ideXlab platform.
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Hindbrain induction and patterning during early vertebrate development
Cellular and Molecular Life Sciences, 2019Co-Authors: Dale Frank, Dalit Sela-donenfeldAbstract:The Hindbrain is a key relay hub of the central nervous system (CNS), linking the bilaterally symmetric half-sides of lower and upper CNS centers via an extensive network of neural pathways. Dedicated neural assemblies within the Hindbrain control many physiological processes, including respiration, blood pressure, motor coordination and different sensations. During early development, the Hindbrain forms metameric segmented units known as rhombomeres along the antero-posterior (AP) axis of the nervous system. These compartmentalized units are highly conserved during vertebrate evolution and act as the template for adult brainstem structure and function. TALE and HOX homeodomain family transcription factors play a key role in the initial induction of the Hindbrain and its specification into rhombomeric cell fate identities along the AP axis. Signaling pathways, such as canonical-Wnt, FGF and retinoic acid, play multiple roles to initially induce the Hindbrain and regulate Hox gene-family expression to control rhombomeric identity. Additional transcription factors including Krox20, Kreisler and others act both upstream and downstream to Hox genes, modulating their expression and protein activity. In this review, we will examine the earliest embryonic signaling pathways that induce the Hindbrain and subsequent rhombomeric segmentation via Hox and other gene expression. We will examine how these signaling pathways and transcription factors interact to activate downstream targets that organize the segmented AP pattern of the embryonic vertebrate Hindbrain.
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Hindbrain induction and patterning during early vertebrate development.
Cellular and molecular life sciences : CMLS, 2018Co-Authors: Dale Frank, Dalit Sela-donenfeldAbstract:The Hindbrain is a key relay hub of the central nervous system (CNS), linking the bilaterally symmetric half-sides of lower and upper CNS centers via an extensive network of neural pathways. Dedicated neural assemblies within the Hindbrain control many physiological processes, including respiration, blood pressure, motor coordination and different sensations. During early development, the Hindbrain forms metameric segmented units known as rhombomeres along the antero-posterior (AP) axis of the nervous system. These compartmentalized units are highly conserved during vertebrate evolution and act as the template for adult brainstem structure and function. TALE and HOX homeodomain family transcription factors play a key role in the initial induction of the Hindbrain and its specification into rhombomeric cell fate identities along the AP axis. Signaling pathways, such as canonical-Wnt, FGF and retinoic acid, play multiple roles to initially induce the Hindbrain and regulate Hox gene-family expression to control rhombomeric identity. Additional transcription factors including Krox20, Kreisler and others act both upstream and downstream to Hox genes, modulating their expression and protein activity. In this review, we will examine the earliest embryonic signaling pathways that induce the Hindbrain and subsequent rhombomeric segmentation via Hox and other gene expression. We will examine how these signaling pathways and transcription factors interact to activate downstream targets that organize the segmented AP pattern of the embryonic vertebrate Hindbrain.
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A novel role for Pax6 in the segmental organization of the Hindbrain
Development (Cambridge England), 2013Co-Authors: Galya Kayam, Claude Brodski, Ayelet Kohl, Zohar Magen, Yuval Peretz, Karen Weisinger, Avi Bar, Orna Novikov, Dalit Sela-donenfeldAbstract:Complex patterns and networks of genes coordinate rhombomeric identities, Hindbrain segmentation and neuronal differentiation and are responsible for later brainstem functions. Pax6 is a highly conserved transcription factor crucial for neuronal development, yet little is known regarding its early roles during Hindbrain segmentation. We show that Pax6 expression is highly dynamic in rhombomeres, suggesting an early function in the Hindbrain. Utilization of multiple gain- and loss-of-function approaches in chick and mice revealed that loss of Pax6 disrupts the sharp expression borders of Krox20, Kreisler, Hoxa2, Hoxb1 and EphA and leads to their expansion into adjacent territories, whereas excess Pax6 reduces these expression domains. A mutual negative cross-talk between Pax6 and Krox20 allows these genes to be co-expressed in the Hindbrain through regulation of the Krox20-repressor gene Nab1 by Pax6. Rhombomere boundaries are also distorted upon Pax6 manipulations, suggesting a mechanism by which Pax6 acts to set Hindbrain segmentation. Finally, FGF signaling acts upstream of the Pax6-Krox20 network to regulate Pax6 segmental expression. This study unravels a novel role for Pax6 in the segmental organization of the early Hindbrain and provides new evidence for its significance in regional organization along the central nervous system.