Rhombomere

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Andrew Lumsden - One of the best experts on this subject based on the ideXlab platform.

  • ral ssBioMed CentNeural Development
    2016
    Co-Authors: David Chambers, Andrew Lumsden, Fabienne Alfonsi, Ewan Hunter, Uma Saxena, Eric Blanc, Leigh Jane Wilson
    Abstract:

    Rhombomere-specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrai

  • Rhombomere specific analysis reveals the repertoire of genetic cues expressed across the developing hindbrain
    Neural Development, 2009
    Co-Authors: David J Chambers, Leigh Wilson, Fabienne Alfonsi, Ewan Hunter, Uma Saxena, Eric Blanc, Andrew Lumsden
    Abstract:

    The Hox family of homeodomain transcription factors comprises pivotal regulators of cell specification and identity during animal development. However, despite their well-defined roles in the establishment of anteroposterior pattern and considerable research into their mechanism of action, relatively few target genes have been identified in the downstream regulatory network. We have sought to investigate this issue, focussing on the developing hindbrain and the cranial motor neurons that arise from this region. The reiterated anteroposterior compartments of the developing hindbrain (Rhombomeres (r)) are normally patterned by the combinatorial action of distinct Hox genes. Alteration in the normal pattern of Hox cues in this region results in a transformation of cellular identity to match the remaining Hox profile, similar to that observed in Drosophila homeotic transformations. To define the repertoire of genes regulated in each Rhombomere, we have analysed the transcriptome of each Rhombomere from wild-type mouse embryos and not those where pattern is perturbed by gain or loss of Hox gene function. Using microarray and bioinformatic methodologies in conjunction with other confirmatory techniques, we report here a detailed and comprehensive set of potential Hox target genes in r2, r3, r4 and r5. We have demonstrated that the data produced are both fully reflective and predictive of Rhombomere identity and, thus, may represent some the of Hox targets. These data have been interrogated to generate a list of candidate genes whose function may contribute to the generation of neuronal subtypes characteristic of each Rhombomere. Interestingly, the data can also be classified into genetic motifs that are predicted by the specific combinations of Hox genes and other regulators of hindbrain anteroposterior identity. The sets of genes described in each or combinations of Rhombomeres span a wide functional range and suggest that the Hox genes, as well as other regulatory inputs, exert their influence across the full spectrum of molecular machinery. We have performed a systematic survey of the transcriptional status of individual segments of the developing mouse hindbrain and identified hundreds of previously undescribed genes expressed in this region. The functional range of the potential candidate effectors or upstream modulators of Hox activity suggest multiple unexplored mechanisms. In particular, we present evidence of a potential new retinoic acid signalling system in ventral r4 and propose a model for the refinement of identity in this region. Furthermore, the Rhombomeres demonstrate a molecular relationship to each other that is consistent with known observations about neurogenesis in the hindbrain. These findings give the first genome-wide insight into the complexity of gene expression during patterning of the developing hindbrain.

  • Rhombomere interactions control the segmental differentiation of hindbrain neurons.
    Molecular and cellular neurosciences, 2001
    Co-Authors: Britta J. Eickholt, Andrew Lumsden, Anthony Graham, Andrea Wizenmann
    Abstract:

    The embryonic hindbrain is subdivided into a series of metameric units termed Rhombomeres, which display features that strongly suggest they are autonomous developmental units. However, some aspects of their phenotype develop nonautonomously. Here we have analyzed the possibility that interRhombomere interactions generate the pattern of segmental neuronal differentiation. The differentiation of both projection interneurons and motor neurons in the hindbrain is retarded in Rhombomeres 3 and 5. We demonstrate here that if either Rhombomere 3 or 5 is isolated from the influence of their neighbours, either in vitro or in vivo, then these segments no longer display delayed neuronal diufferentiation. We further show that the retardation of motor neurons differentiation in Rhombomeres 3 and 5 is, at least in part, mediated by Bmp-4. If this molecule is inhibited, by grafting cells expressing chordin, then the motor neurons of these Rhombomeres develop ahead of their normal schedule.

  • Closing in on Rhombomere boundaries
    Nature Cell Biology, 1999
    Co-Authors: Andrew Lumsden
    Abstract:

    Eph receptors and their membrane-bound ephrin ligands are expressed in complementary segments of the hindbrain. Signalling between these receptors and ligands is sufficient to establish a sharp boundary between adjacent segments and to prevent cell mixing.

  • Homeotic Transformation of Rhombomere Identity After Localized Hoxb1 Misexpression
    Science (New York N.Y.), 1999
    Co-Authors: Esther Bell, Richard J. T. Wingate, Andrew Lumsden
    Abstract:

    Segmentation of the hindbrain and branchial region is a conserved feature of head development, involving the nested expression of Hox genes. Although it is presumed that vertebrate Hox genes function as segment identifiers, responsible for mediating registration between elements of diverse embryonic origin, this assumption has remained untested. To assess this, retroviral misexpression was combined with orthotopic grafting in chick embryos to generate a mismatch in Hox coding between a specific Rhombomere and its corresponding branchial arch. Rhombomere-restricted misexpression of a single gene, Hoxb1, resulted in the homeotic transformation of the Rhombomere, revealed by reorganization of motor axon projections.

Patrick Charnay - One of the best experts on this subject based on the ideXlab platform.

  • Krox20 hindbrain regulation incorporates multiple modes of cooperation between cis-acting elements
    PLoS Genetics, 2017
    Co-Authors: Elodie Thierion, Patrick Charnay, Johan Le Men, Samuel Collombet, Céline Hernandez, Fanny Coulpier, Patrick Torbey, Morgane Thomas-chollier, Daan Noordermeer, Pascale Gilardi-hebenstreit
    Abstract:

    Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes a transcription factor required for the specification of two segments (Rhombomeres) of the developing hindbrain. In Rhombomere 3, Krox20 is subject to direct positive feedback governed by an autoregulatory enhancer, element A. In contrast, a second enhancer, element C, distant by 70 kb, is active from the initiation of transcription independent of the presence of the KROX20 protein. Here, using both enhancer knock-outs and investigations of chromatin organisation, we show that element C possesses a dual activity: besides its classical enhancer function, it is also permanently required in cis to potentiate the autoregulatory activity of element A, by increasing its chromatin accessibility. This work uncovers a novel, asymmetrical, long-range mode of cooperation between cis-acting elements that might be essential to avoid promiscuous activation of positive autoregulatory elements.

  • Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening.
    Neural Development, 2007
    Co-Authors: Fabrice Chatonnet, Emmanuel Taillebourg, Patrick Charnay, Massimo Pasqualetti, Filippo M Rijli, Ludovic Wrobel, Valerie Mezieres, Sebastien Ducret, Jean Champagnat
    Abstract:

    ABSTRACT: BACKGROUND: Little is known about the involvement of molecular determinants of segmental patterning of Rhombomeres (r) in the development of rhythmic neural networks in the mouse hindbrain. Here, we compare the phenotypes of mice carrying targeted inactivations of Hoxa2, the only Hox gene expressed up to r2, and of Krox20, expressed in r3 and r5. We investigated the impact of such mutations on the neural circuits controlling jaw opening and breathing in newborn mice, compatible with Hoxa2-dependent trigeminal defects and direct regulation of Hoxa2 by Krox20 in r3. RESULTS: We found that Hoxa2 mutants displayed an impaired oro-buccal reflex, similarly to Krox20 mutants. In contrast, while Krox20 is required for the development of the rhythm-promoting parafacial respiratory group (pFRG) modulating respiratory frequency, Hoxa2 inactivation did not affect neonatal breathing frequency. Instead, we found that Hoxa2-/- but not Krox20-/- mutation leads to the elimination of a transient control of the inspiratory amplitude normally occurring during the first hours following birth. Tracing of r2-specific progenies of Hoxa2 expressing cells indicated that the control of inspiratory activity resides in rostral pontine areas and required an intact r2-derived territory. CONCLUSIONS: Thus, inspiratory shaping and respiratory frequency are under the control of distinct Hox-dependent segmental cues in the mammalian brain. Moreover, these data point to the importance of Rhombomere-specific genetic control in the development of modular neural networks in the mammalian hindbrain.

  • Hoxa2- and Rhombomere-dependent development of the mouse facial somatosensory map.
    Science, 2006
    Co-Authors: Franck Oury, Patrick Charnay, Yasunori Murakami, Jean-sebastien Renaud, Massimo Pasqualetti, Shu-yue Ren, Filippo M Rijli
    Abstract:

    In the mouse trigeminal pathway, sensory inputs from distinct facial structures, such as whiskers or lower jaw and lip, are topographically mapped onto the somatosensory cortex through relay stations in the thalamus and hindbrain. In the developing hindbrain, the mechanisms generating such maps remain elusive. We found that in the principal sensory nucleus, the whisker-related map is contributed by Rhombomere 3-derived neurons, whereas the Rhombomere 2-derived progeny supply the lower jaw and lip representation. Moreover, early Hoxa2 expression in neuroepithelium prevents the trigeminal nerve from ectopically projecting to the cerebellum, whereas late expression in the principal sensory nucleus promotes selective arborization of whisker-related afferents and topographic connectivity to the thalamus. Hoxa2 inactivation further results in the absence of whisker-related maps in the postnatal brain. Thus, Hoxa2- and Rhombomere 3-dependent cues determine the whisker area map and are required for the assembly of the whisker-to-barrel somatosensory circuit.

  • Novel Activities of Mafb Underlie Its Dual Role in Hindbrain Segmentation and Regional Specification
    Developmental Biology, 2003
    Co-Authors: François Giudicelli, Pascale Gilardi-hebenstreit, Fatima Mechta-grigoriou, Christophe Poquet, Patrick Charnay
    Abstract:

    The bZip transcription factor Mafb is expressed in two segments of the developing vertebrate hindbrain: the Rhombomeres 5 and 6. Loss of Mafb expression in the mouse mutant kreisler leads to elimination of r5 and to alterations of r6 regional identity. Here, we further investigated the role of Mafb in hindbrain patterning using gain-of-function experiments in the chick embryo. Our work has revealed novel functions for Mafb, including a positive autoregulatory activity, the capacity to repress Hoxb1 expression, and the capacity to synergise with or antagonise Krox20 activity. These different activities appear to be spatially restricted in the hindbrain, presumably due to interactions with other factors. Reinvestigation of the kreisler mutation indicated that it also results in an ectopic activation of Mafb in Rhombomere 3, accounting for the previously described molecular alterations of this Rhombomere in the mutant. Together, these data allow us to refine our view of the dual function of Mafb in both segmentation and specification of anteroposterior identity in the hindbrain.

  • hindbrain patterning krox20 couples segmentation and specification of regional identity
    Development, 2001
    Co-Authors: Octavian Voiculescu, Emmanuel Taillebourg, Cristina Pujades, Stéphanie Buart, Chantal Kress, Patrick Charnay, Sylvie Schneidermaunoury
    Abstract:

    We have previously demonstrated that inactivation of the Krox20 gene led to the disappearance of its segmental expression territories in the hindbrain, the Rhombomeres (r) 3 and 5. We now performed a detailed analysis of the fate of prospective r3 and r5 cells in Krox20 mutant embryos. Genetic fate mapping indicates that at least some of these cells persist in the absence of a functional Krox20 protein and uncovers the requirement for autoregulatory mechanisms in the expansion and maintenance of Krox20-expressing territories. Analysis of even-numbered Rhombomere molecular markers demonstrates that in Krox20-null embryos, r3 cells acquire r2 or r4 identity, and r5 cells acquire r6 identity. Finally, study of embryonic chimaeras between Krox20 homozygous mutant and wild-type cells shows that the mingling properties of r3/r5 mutant cells are changed towards those of even-numbered Rhombomere cells. Together, these data demonstrate that Krox20 is essential to the generation of alternating odd- and even-numbered territories in the hindbrain and that it acts by coupling the processes of segment formation, cell segregation and specification of regional identity.

Filippo M Rijli - One of the best experts on this subject based on the ideXlab platform.

  • integrating into the Rhombomere community across the border
    Developmental Cell, 2018
    Co-Authors: Taro Kitazawa, Filippo M Rijli
    Abstract:

    During early hindbrain development, single neuroepithelial progenitors cross into neighboring Rhombomere compartments and switch their molecular identity to match their new position. In this issue of Developmental Cell,Addison et al. (2018) show that this identity switch is mediated by non-cell-autonomous retinoid signaling that ensures a homogeneous segment identity.

  • Distinct roles of Hoxa2 and Krox20 in the development of rhythmic neural networks controlling inspiratory depth, respiratory frequency, and jaw opening.
    Neural Development, 2007
    Co-Authors: Fabrice Chatonnet, Emmanuel Taillebourg, Patrick Charnay, Massimo Pasqualetti, Filippo M Rijli, Ludovic Wrobel, Valerie Mezieres, Sebastien Ducret, Jean Champagnat
    Abstract:

    ABSTRACT: BACKGROUND: Little is known about the involvement of molecular determinants of segmental patterning of Rhombomeres (r) in the development of rhythmic neural networks in the mouse hindbrain. Here, we compare the phenotypes of mice carrying targeted inactivations of Hoxa2, the only Hox gene expressed up to r2, and of Krox20, expressed in r3 and r5. We investigated the impact of such mutations on the neural circuits controlling jaw opening and breathing in newborn mice, compatible with Hoxa2-dependent trigeminal defects and direct regulation of Hoxa2 by Krox20 in r3. RESULTS: We found that Hoxa2 mutants displayed an impaired oro-buccal reflex, similarly to Krox20 mutants. In contrast, while Krox20 is required for the development of the rhythm-promoting parafacial respiratory group (pFRG) modulating respiratory frequency, Hoxa2 inactivation did not affect neonatal breathing frequency. Instead, we found that Hoxa2-/- but not Krox20-/- mutation leads to the elimination of a transient control of the inspiratory amplitude normally occurring during the first hours following birth. Tracing of r2-specific progenies of Hoxa2 expressing cells indicated that the control of inspiratory activity resides in rostral pontine areas and required an intact r2-derived territory. CONCLUSIONS: Thus, inspiratory shaping and respiratory frequency are under the control of distinct Hox-dependent segmental cues in the mammalian brain. Moreover, these data point to the importance of Rhombomere-specific genetic control in the development of modular neural networks in the mammalian hindbrain.

  • Fate-mapping the mammalian hindbrain: segmental origins of vestibular projection neurons assessed using Rhombomere-specific Hoxa2 enhancer elements in the mouse embryo.
    Journal of Neuroscience, 2007
    Co-Authors: Massimo Pasqualetti, Jean-sebastien Renaud, Filippo M Rijli, Carmen Díaz, Joel C Glover
    Abstract:

    As a step toward generating a fate map of identified neuron populations in the mammalian hindbrain, we assessed the contributions of individual Rhombomeres to the vestibular nuclear complex, a major sensorimotor area that spans the entire rhombencephalon. Transgenic mice harboring either the lacZ or the enhanced green fluorescent protein reporter genes under the transcriptional control of Rhombomere-specific Hoxa2 enhancer elements were used to visualize Rhombomere-derived domains. We labeled functionally identifiable vestibular projection neuron groups retrogradely with conjugated dextran-amines at successive embryonic stages and obtained developmental fate maps through direct comparison with the Rhombomere-derived domains in the same embryos. The fate maps show that each vestibular neuron group derives from a unique rostrocaudal domain that is relatively stable developmentally, suggesting that anteroposterior migration is not a major contributor to the rostrocaudal patterning of the vestibular system. Most of the groups are multisegmental in origin, and each Rhombomere is fated to give rise to two or more vestibular projection neuron types, in a complex pattern that is not segmentally iterated. Comparison with studies in the chicken embryo shows that the rostrocaudal patterning of identified vestibular projection neuron groups is generally well conserved between avians and mammalians but that significant species-specific differences exist in the rostrocaudal limits of particular groups. This mammalian hindbrain fate map can be used as the basis for targeting genetic manipulation to specific subpopulations of vestibular projection neurons.

  • Hoxa2- and Rhombomere-dependent development of the mouse facial somatosensory map.
    Science, 2006
    Co-Authors: Franck Oury, Patrick Charnay, Yasunori Murakami, Jean-sebastien Renaud, Massimo Pasqualetti, Shu-yue Ren, Filippo M Rijli
    Abstract:

    In the mouse trigeminal pathway, sensory inputs from distinct facial structures, such as whiskers or lower jaw and lip, are topographically mapped onto the somatosensory cortex through relay stations in the thalamus and hindbrain. In the developing hindbrain, the mechanisms generating such maps remain elusive. We found that in the principal sensory nucleus, the whisker-related map is contributed by Rhombomere 3-derived neurons, whereas the Rhombomere 2-derived progeny supply the lower jaw and lip representation. Moreover, early Hoxa2 expression in neuroepithelium prevents the trigeminal nerve from ectopically projecting to the cerebellum, whereas late expression in the principal sensory nucleus promotes selective arborization of whisker-related afferents and topographic connectivity to the thalamus. Hoxa2 inactivation further results in the absence of whisker-related maps in the postnatal brain. Thus, Hoxa2- and Rhombomere 3-dependent cues determine the whisker area map and are required for the assembly of the whisker-to-barrel somatosensory circuit.

  • hoxa2 and hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain
    Neuron, 1999
    Co-Authors: Marc Davenne, Pierre Chambon, Mark Maconochie, Rudiger Neun, Alexandre Pattyn, Robb Krumlauf, Filippo M Rijli
    Abstract:

    Little is known about how the generation of specific neuronal types at stereotypic positions within the hindbrain is linked to Hox gene-mediated patterning. Here, we show that during neurogenesis, Hox paralog group 2 genes control both anteroposterior (A-P) and dorsoventral (D-V) patterning. Hoxa2 and Hoxb2 differentially regulate, in a Rhombomere-specific manner, the expression of several genes in broad D-V-restricted domains or narrower longitudinal columns of neuronal progenitors, immature neurons, and differentiating neuronal subtypes. Moreover, Hoxa2 and Hoxb2 can functionally synergize in controlling the development of ventral neuronal subtypes in Rhombomere 3 (r3). Thus, in addition to their roles in A-P patterning, Hoxa2 and Hoxb2 have distinct and restricted functions along the D-V axis during neurogenesis, providing insights into how neuronal fates are assigned at stereotypic positions within the hindbrain.

Sarah Guthrie - One of the best experts on this subject based on the ideXlab platform.

  • Ephrin-As play a Rhombomere-specific role in trigeminal motor axon projections in the chick embryo
    Developmental biology, 2005
    Co-Authors: Fabrice Prin, Uma Thaker, Uwe Drescher, Sarah Guthrie
    Abstract:

    In this study, we investigate the possible role of ephrin–Eph signaling in trigeminal motor axon projections. We find that EphA receptors are expressed at higher levels by Rhombomere 2 (r2) trigeminal motor neurons than by r3 trigeminal motor neurons in the chick embryo. Mapping of Rhombomere-specific axon projections shows that r2 and r3 trigeminal motor neurons project to different muscle targets, including the mandibular adductor and the intermandibularis muscles respectively. Ephrin-A5 is expressed in these muscles, especially in some regions of the intermandibularis muscle, and can cause growth cone collapse of both r2 and r3 motor axons in vitro. We demonstrate that in vivo overexpression of ephrin-A5 in the intermandibularis muscle, or overexpression of dominant-negative EphA receptors in trigeminal motor neurons leads to a reduction in branching of r3-derived motor axons specifically. Overexpression of full-length EphA receptors impairs the formation of r3 projections to the intermandibularis muscle. These findings indicate that ephrins and their Eph receptors play a role in trigeminal motor axon topographic mapping and in Rhombomere 3-derived projections in particular.

  • Rhombomere origin plays a role in the specificity of cranial motor axon projections in the chick.
    The European journal of neuroscience, 1999
    Co-Authors: Joanne Warrilow, Sarah Guthrie
    Abstract:

    Guidance of cranial motor axons to their targets conforms to a segmental plan in the chick embryo. Trigeminal motor neurons lie within Rhombomeres 2 and 3 and project via an exit point in Rhombomere 2 to innervate the first branchial arch. Facial motor neurons lie within Rhombomeres 4 and 5 and grow out via an exit point in Rhombomere 4 to innervate the second branchial arch. We have investigated the axial level-specific matching of motor neurons and branchial arches using donor to host transplantation in avian embryos. Previous work has shown that rostrocaudal reversal of a single hindbrain segment (Rhombomere 3) leads to misprojection of a contingent of trigeminal axons via the facial nerve exit point. Using the same experimental manipulation in chick embryos and quail–chick chimaeras, we have analysed the pathways of these aberrant projections. We have found that in the majority of embryos analysed from stage 19 to 31, trigeminal axons from the transplanted Rhombomere projected towards second branchial arch muscles, in addition to their normal first arch muscle targets. However, from stage 32 to 36, aberrant projections to second arch-derived muscles were detected only in a small minority of embryos. These experiments show that trigeminal motor neurons show a lack of specificity in their early projection into the periphery but that inappropriate projections may be later eliminated. This suggests that segmental mechanisms intrinsic to the hindbrain specify motor neurons with respect to their eventual innervation pattern.

  • selective dispersal of avian Rhombomere cells in orthotopic and heterotopic grafts
    Development, 1993
    Co-Authors: Sarah Guthrie, Victoria E Prince, Andrew Lumsden
    Abstract:

    During hindbrain development, cells become segregated into segmental groups, Rhombomeres, by mechanisms that are presently unknown. One contributory factor early in development may be an alternating periodicity in cell surface properties down the neuraxis. This possibility was previously suggested by experiments in which tissue from different segmental levels was apposed in the absence of a boundary. New boundaries were regenerated only when Rhombomeres from adjacent positions or positions three Rhombomeres distant from one another were apposed. Combinations of two odd-numbered or two even-numbered Rhombomeres usually failed to generate a boundary. In order to pursue this phenomenon to the cellular level, we have used two approaches, both involving donor-to-host transplantation. First, quail Rhombomeres were grafted at various hindbrain levels of a chick host. Apposition of Rhombomere 4 (r4) with r3 was concomitant with negligible cell mixing across the interface. By contrast, combinations of r3 with r5 or with r3 tissue led to cell mixing that was more extensive in combinations of identical Rhombomeres (r3 with r3) than between two alternate ones (r3 with r5). Secondly, we grafted small pieces of fluorescently prelabelled chick Rhombomere tissue at various hindbrain levels of chick hosts. In most cases, cells dispersed widely when transplanted orthopically or two segments distant from that of their origin. Cells transplanted into an adjacent segment, however, showed a tendency to remain undispersed. Among the different graft combinations, furthermore, there was a variation in the extent of dispersal that showed an additional level of complexity not revealed in boundary regeneration experiments. The possibility is raised that the early partitioning of Rhombomeres involves a hierarchy in the adhesive preferences of cell-cell interactions along the neuraxis.

  • neuroectodermal autonomy of hox 2 9 expression revealed by Rhombomere transpositions
    Nature, 1992
    Co-Authors: Sarah Guthrie, Robb Krumlauf, Heather Marshall, Atsushi Kuroiwa, Ian Muchamore, Andrew Lumsden
    Abstract:

    INVOLVEMENT of the Hox genes in regional specifications of the vertebrate body axis is suggested by sequence similarity with the homeotic selector genes of Drosophila, the conservation of a collinear relationship between genomic organization and site of expression, and mutational analysis1–5. Subdivision of vertebrate embryo hindbrain neuroepithelium into lineage compartments6 (Rhombomeres7,8) underlies segmental patterning of neuronal differentiation9. The Rhombomere boundaries delimit domains of expression of Hox genes10–12, presumed to be determinants of Rhombomere phenotype, suggesting that Hox genes confer positional value13; the formation of Rhombomere 4 (r4) is followed by strong expression of Hox-2.9within its confines14. If the Hox genes are determinants, their expression should be autonomous from the developmental stage at which regional commitment becomes fixed and irreversible. We have transplanted the future r4 region (from state-9 – chick embryos) into the more anterior position of r2 and probed for Hox-2.9 transcripts. We report here that Hox-2.9 was expressed in the ectopic r4 as strongly as in the normal r4, whereas reciprocal grafts of future r2 to r4 position did not express Hox-2.9. The phenotype of ectopic Rhombomeres developed according to their original position, as demonstrated by retrograde tracing of efferent cranial nerve nuclei. As early as stage-9 – (six somites), both Hox-2.9 expression and segment identity are autonomous in the chick embryo hindbrain, independent both of position in the neuroepithelium and of signals from the underlying mesoderm15.

  • Motor neuron pathfinding following Rhombomere reversals in the chick embryo hindbrain.
    Development (Cambridge England), 1992
    Co-Authors: Sarah Guthrie, Andrew Lumsden
    Abstract:

    Motor neurons are segmentally organised in the developing chick hindbrain, with groups of neurons occupying pairs of hindbrain segments or Rhombomeres. The branchiomotor nucleus of the trigeminal nerve occupies Rhombomeres 2 and 3 (r2 and r3), that of the facial nerve r4 and r5, and that of the glossopharyngeal nerve r6 and r7. Branchiomotor neuron cell bodies lie within the basal plate, forming columns on either side of the ventral midline floor plate. Axons originating in Rhombomeres 2, 4 and 6 grow laterally (dorsally) towards the exit points located in the alar plates of these Rhombomeres, while axons originating in odd-numbered Rhombomeres 3 and 5 grow laterally and then rostrally, crossing a Rhombomere boundary to reach their exit point. Examination of the trajectories of motor axons in odd-numbered segments at late stages of development (19–25) showed stereotyped pathways, in which axons grew laterally before making a sharp turn rostrally. During the initial phase of outgrowth (stage 14–15), however, axons had meandering courses and did not grow in a directed fashion towards their exit point. When r3 or r5 was transplanted with reversed rostrocaudal polarity prior to motor axon outgrowth, the majority of axons grew to their appropriate, rostral exit point, despite the inverted neuroepithelial polarity. In r3 reversals, however, there was a considerable increase in the normally small number of axons that grew out via the caudal, r4 exit point. These findings are discussed with relevance to the factors involved in motor neuron specification and axon outgrowth in the developing hindbrain.

Robb Krumlauf - One of the best experts on this subject based on the ideXlab platform.

  • hoxa2 and hoxb2 control dorsoventral patterns of neuronal development in the rostral hindbrain
    Neuron, 1999
    Co-Authors: Marc Davenne, Pierre Chambon, Mark Maconochie, Rudiger Neun, Alexandre Pattyn, Robb Krumlauf, Filippo M Rijli
    Abstract:

    Little is known about how the generation of specific neuronal types at stereotypic positions within the hindbrain is linked to Hox gene-mediated patterning. Here, we show that during neurogenesis, Hox paralog group 2 genes control both anteroposterior (A-P) and dorsoventral (D-V) patterning. Hoxa2 and Hoxb2 differentially regulate, in a Rhombomere-specific manner, the expression of several genes in broad D-V-restricted domains or narrower longitudinal columns of neuronal progenitors, immature neurons, and differentiating neuronal subtypes. Moreover, Hoxa2 and Hoxb2 can functionally synergize in controlling the development of ventral neuronal subtypes in Rhombomere 3 (r3). Thus, in addition to their roles in A-P patterning, Hoxa2 and Hoxb2 have distinct and restricted functions along the D-V axis during neurogenesis, providing insights into how neuronal fates are assigned at stereotypic positions within the hindbrain.

  • genetic interactions between hoxa1 and hoxb1 reveal new roles in regulation of early hindbrain patterning
    Development, 1998
    Co-Authors: Michele Studer, Filippo M Rijli, Pierre Chambon, Heather Marshall, Anthony Gavalas, Linda Arizamcnaughton, Robb Krumlauf
    Abstract:

    In the developing vertebrate hindbrain Hoxa1 and Hoxb1 play important roles in patterning segmental units (Rhombomeres). In this study, genetic analysis of double mutants demonstrates that both Hoxa1 and Hoxb1 participate in the establishment and maintenance of Hoxb1 expression in Rhombomere 4 through auto- and para-regulatory interactions. The generation of a targeted mutation in a Hoxb1 3′ retinoic acid response element (RARE) shows that it is required for establishing early high levels of Hoxb1 expression in neural ectoderm. Double mutant analysis with this Hoxb1(3′RARE) allele and other targeted loss-of-function alleles from both Hoxa1 and Hoxb1 reveals synergy between these genes. In the absence of both genes, a territory appears in the region of r4, but the earliest r4 marker, the Eph tyrosine kinase receptor EphA2, fails to be activated. This suggests a failure to initiate rather than maintain the specification of r4 identity and defines new roles for both Hoxb1 and Hoxa1 in early patterning events in r4. Our genetic analysis shows that individual members of the vertebrate labial-related genes have multiple roles in different steps governing segmental processes in the developing hindbrain.

  • reprogramming hox expression in the vertebrate hindbrain influence of paraxial mesoderm and Rhombomere transposition
    Neuron, 1996
    Co-Authors: Nobue Itasaki, James Sharpe, Alastair Morrison, Robb Krumlauf
    Abstract:

    Abstract The developing vertebrate hindbrain consists of segments known as Rhombomeres, which express combinations of Hox genes implicated in specifying segmental identity. Using chick–chick and chick– transgenic mouse graftings, we show that anterior to posterior Rhombomere transpositions result in a progressive posterior transformation and coordinate induction of new Hox expression. This shows that hindbrain plasticity is evolutionarily conserved and implies Rhombomeres may be undergoing continual assessment of their identities. The nature of the changes is dependent on both the anteroposterior position of the graft and its origin. Transposed somites from specific axial levels and developmental stages have a graded ability to induce changes in Hox expression, indicating that paraxial mesoderm is a source of the environmental signal responsible for the plasticity.

  • Rhombomere of origin determines autonomous versus environmentally regulated expression of hoxa 3 in the avian embryo
    Development, 1996
    Co-Authors: Jose R Saldivar, Robb Krumlauf, Linda Arizamcnaughton, Catherine E Krull, Marianne Bronnerfraser
    Abstract:

    We have investigated the pattern and regulation of Hoxa3 expression in the hindbrain and associated neural crest cells in the chick embryo, using whole mount in situ hybridization in conjunction with DiI labeling of neural crest cells and microsurgical manipulations. Hoxa3 is expressed in the neural plate and later in the neural tube with a rostral border of expression corresponding to the boundary between Rhombomeres (r) 4 and 5. Initial expression is diffuse and becomes sharp after boundary formation. Hoxa3 exhibits uniform expression within r5 after formation of rhombomeric borders. Cell marking experiments reveal that neural crest cells migrating caudally, but not rostrally, from r5 and caudally from r6 express Hoxa3 in normal embryo. Results from transposition experiments demonstrate that expression of Hoxa3 in r5 neural crest cells is not strictly cell-autonomous. When r5 is transposed with r4 by rostrocaudal rotation of the rhomobomeres, Hoxa3 is expressed in cells migrating lateral to transposed r5 and for a short time, in condensing ganglia, but not by neural crest within the second branchial arch. Since DiI-labeled cells from transposed r5 are present in the second arch, Hoxa3-expressing neural crest cells from r5 appear to down-regulate their Hoxa3 expression in their new environment. In contrast, when r6 is transposed to the position of r4 after boundary formation, Hoxa3 is maintained in both migrating neural crest cells and those positioned within the second branchial arch and associated ganglia. These results suggest that Hoxa3 expression is cell-autonomous in r6 and its associated neural crest. Our results suggest that neural crest cells expressing the same Hox gene are not eqivalent; they respond differently to environmental signals and exhibit distinct degrees of cell autonomy depending upon their Rhombomere of origin.

  • role of a conserved retinoic acid response element in Rhombomere restriction of hoxb 1
    Science, 1994
    Co-Authors: Michele Studer, Heather Marshall, Heike Popperl, Atsushi Kuroiwa, Robb Krumlauf
    Abstract:

    After activation in mesoderm and neuroectoderm, expression of the Hoxb-1 gene is progressively restricted to Rhombomere (r) 4 in the hindbrain. Analysis of the chick and mouse Hoxb-1 genes identified positive and negative regulatory regions that cooperate to mediate segment-restricted expression during Rhombomere formation. An enhancer generates expression extending into r3 and r5, and a repressor limits this domain to r4. The repressor contains a conserved retinoic acid response element, point mutations in which allow expression to spread into adjacent Rhombomeres. Retinoids and their nuclear receptors may therefore participate in sharpening segment-restricted expression of Hoxb-1 during Rhombomere boundary formation.

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