Faculty Opinions recommendation of The role of the rhombic lip in avian cerebellum development.

2002 ◽  
Author(s):  
Andrew Lumsden
Keyword(s):  
Cerebellum Development ◽  
Rhombic Lip

scholarly journals The role of the rhombic lip in avian cerebellum development

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4395-4404 ◽  
Author(s):  
R.J. Wingate ◽  
M.E. Hatten
Keyword(s):  
Axon Guidance ◽  
Granule Cell ◽  
Fate Mapping ◽  
Germinal Layer ◽  
Pontine Nucleus ◽  
Dorsoventral Axis ◽  
Cerebellum Development ◽  
Mapping Techniques ◽  
Rhombic Lip

We have used a combination of quail-chick fate-mapping techniques and dye labelling to investigate the development of the avian cerebellum. Using Hoxa2 as a guide for the microsurgical construction of quail-chick chimaeras, we show that the caudal boundary of the presumptive cerebellum at E6 maps to the caudal boundary of rhombomere 1. By fate mapping the dorsoventral axis of rhombomere 1, we demonstrate that granule cell precursors are generated at the rhombic lip together with neurons of the lateral pontine nucleus. DiI-labelling of cerebellum explants reveals that external germinal layer precursors have a characteristic unipolar morphology and undergo an orientated, active migration away from the rhombic lip, which is apparently independent of either glial or axon guidance or ‘chain’ formation.

Role of Pax6 in development of the cerebellar system

Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3585-3596 ◽  
Author(s):  
D. Engelkamp ◽  
P. Rashbass ◽  
A. Seawright ◽  
V. van Heyningen
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Granule Cell ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Long Distance ◽  
Cerebellar Granule ◽  
Precerebellar Nuclei ◽  
Rhombic Lip

Post-mitotic neurons generated at the rhombic lip undertake long distance migration to widely dispersed destinations, giving rise to cerebellar granule cells and the precerebellar nuclei. Here we show that Pax6, a key regulator in CNS and eye development, is strongly expressed in rhombic lip and in cells migrating away from it. Development of some structures derived from these cells is severely affected in Pax6-null Small eye (Pax6(Sey)/Pax6(Sey)) embryos. Cell proliferation and initial differentiation seem unaffected, but cell migration and neurite extension are disrupted in mutant embryos. Three of the five precerebellar nuclei fail to form correctly. In the cerebellum the pre-migratory granule cell sub-layer and fissures are absent. Some granule cells are found in ectopic positions in the inferior colliculus which may result from the complete absence of Unc5h3 expression in Pax6(Sey)/Pax6(Sey) granule cells. Our results suggest that Pax6 plays a strong role during hindbrain migration processes and at least part of its activity is mediated through regulation of the netrin receptor Unc5h3.

scholarly journals The specification of noradrenergic locus coeruleus (LC) neurones depends on bone morphogenetic proteins (BMPs)

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 983-991 ◽  
Author(s):  
Astrid Vogel-Höpker ◽  
Hermann Rohrer
Keyword(s):  
Transcription Factors ◽  
Locus Coeruleus ◽  
Bone Morphogenetic Proteins ◽  
Chick Embryos ◽  
Dorsal Midline ◽  
Neural Crest Development ◽  
Roof Plate ◽  
Rhombic Lip ◽  
The Brain

The role of BMPs in the development of the major noradrenergic centre of the brain, the locus coeruleus (LC), was investigated. LC generation is reflected by initial expression of the transcription factors Phox2a and Phox2b in dorsal rhombomere1 (r1), followed by expression of dopamine-β-hydroxylase and tyrosine hydroxylase. Bmp5 is expressed in the dorsal neuroepithelium in proximity to Phox2-expressing cells. BMP inhibition in stage 10 chick embryos resulted in the lack of LC neurones or in their generation at the dorsal midline, and loss of roof plate and rhombic lip, but it did not affect neural crest development. These results reveal late essential BMP functions in the specification of dorsal neuronal phenotypes in r1, including LC neurones, and in the development of dorsal midline structures.

scholarly journals Unipolar (Dendritic) Brush Cells Are Morphologically Complex and Require Tbr2 for Differentiation and Migration

2021 ◽  
Vol 14 ◽  
Author(s):  
Ashley McDonough ◽  
Gina E. Elsen ◽  
Ray M. Daza ◽  
Amelia R. Bachleda ◽  
Donald Pizzo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Specific Expression ◽  
Brush Cells ◽  
Knock Out ◽  
Unipolar Brush Cells ◽  
Human Cerebellum ◽  
And Migration ◽  
Rhombic Lip ◽  
Mouse Lines

Previous studies demonstrated specific expression of transcription factor Tbr2 in unipolar brush cells (UBCs) of the cerebellum during development and adulthood. To further study UBCs and the role of Tbr2 in their development we examined UBC morphology in transgenic mouse lines (reporter and lineage tracer) and also examined the effects of Tbr2 deficiency in Tbr2 (MGI: Eomes) conditional knock-out (cKO) mice. In Tbr2 reporter and lineage tracer cerebellum, UBCs exhibited more complex morphologies than previously reported including multiple dendrites, bifurcating dendrites, and up to four dendritic brushes. We propose that “dendritic brush cells” (DBCs) may be a more apt nomenclature. In Tbr2 cKO cerebellum, mature UBCs were completely absent. Migration of UBC precursors from rhombic lip to cerebellar cortex and other nuclei was impaired in Tbr2 cKO mice. Our results indicate that UBC migration and differentiation are sensitive to Tbr2 deficiency. To investigate whether UBCs develop similarly in humans as in rodents, we studied Tbr2 expression in mid-gestational human cerebellum. Remarkably, Tbr2+ UBC precursors migrate along the same pathways in humans as in rodent cerebellum and disperse to create the same “fountain-like” appearance characteristic of UBCs exiting the rhombic lip.

scholarly journals Functional role of laminin α1 chain during cerebellum development

2011 ◽  
Vol 5 (6) ◽  
pp. 480-489 ◽  
Author(s):  
Celine Heng ◽  
Olivier Lefebvre ◽  
Annick Klein ◽  
Malia Edwards ◽  
Patricia Simon-Assmann ◽  
...  
Keyword(s):  
Functional Role ◽  
Cerebellum Development

scholarly journals The centrosome neither persistently leads migration nor determines the site of axonogenesis in migrating neurons in vivo

2010 ◽  
Vol 191 (4) ◽  
pp. 875-890 ◽  
Author(s):  
Martin Distel ◽  
Jennifer C. Hocking ◽  
Katrin Volkmann ◽  
Reinhard W. Köster
Keyword(s):  
Gene Expression ◽  
Neuronal Migration ◽  
Cell Type ◽  
Vertebrate Brain ◽  
Cell Type Specific ◽  
Positive Correlations ◽  
Experimental Findings ◽  
Rhombic Lip

The position of the centrosome ahead of the nucleus has been considered crucial for coordinating neuronal migration in most developmental situations. The proximity of the centrosome has also been correlated with the site of axonogenesis in certain differentiating neurons. Despite these positive correlations, accumulating experimental findings appear to negate a universal role of the centrosome in determining where an axon forms, or in leading the migration of neurons. To further examine this controversy in an in vivo setting, we have generated cell type–specific multi-cistronic gene expression to monitor subcellular dynamics in the developing zebrafish cerebellum. We show that migration of rhombic lip–derived neurons is characterized by a centrosome that does not persistently lead the nucleus, but which is instead regularly overtaken by the nucleus. In addition, axonogenesis is initiated during the onset of neuronal migration and occurs independently of centrosome proximity. These in vivo data reveal a new temporal orchestration of organelle dynamics and provide important insights into the variation in intracellular processes during vertebrate brain differentiation.

scholarly journals Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum

2017 ◽  
Author(s):  
Chelsea U. Kidwell ◽  
Chen-Ying Su ◽  
Masahiko Hibi ◽  
Cecilia B. Moens
Keyword(s):  
Neuronal Maturation ◽  
Granule Neurons ◽  
Granule Neuron ◽  
Helix Loop Helix ◽  
Neuron Populations ◽  
Full Complement ◽  
Neuronal Types ◽  
Summary Statement ◽  
Rhombic Lip

ABSTRACTThe basic Helix-Loop-Helix transcription factor Atoh1 is required for the specification of multiple neuron types in the mammalian hindbrain including tegmental, precerebellar output neurons and cerebellar granule neurons. How a single proneural gene specifies so many neuron types from a single progenitor zone, the upper rhombic lip (URL), is not known. Here we use the zebrafish to explore the role of atoh1 in cerebellar neurogenesis. Using transgenic reporters we show that zebrafish atoh1c-expressing cells give rise to tegmental and granule cell populations that, together with previously described atoh1a-derived neuron populations, resemble the diversity of atoh1 derivatives observed in mammals. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons in the zebrafish cerebellum. Interestingly, atoh1a and atoh1c specify non-overlapping granule populations, indicating that fish use multiple atoh1 genes to generate granule neuron diversity that is not detected in mammals. By live imaging of neurogenesis at the URL we show that atoh1c is not required for the specification of granule neuron progenitors but promotes their delamination from the URL epithelium and this process is critical for neuronal maturation. This study thus provides a better understanding of how proneural transcription factors regulate neurogenesis in the vertebrate cerebellum.Summary statementatoh1 genes specify distinct populations of tegmental and granule neurons in the zebrafish hindbrain and promote their delamination from the neuroepithelium, a process critical for neuronal maturation.

scholarly journals Erbb4 Is Required for Cerebellar Development and Malignant Phenotype of Medulloblastoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 997
Author(s):  
Juncal Aldaregia ◽  
Peio Errarte ◽  
Ane Olazagoitia-Garmendia ◽  
Marian Gimeno ◽  
Jose Javier Uriz ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Critical Role ◽  
Pediatric Brain Tumor ◽  
Cerebellar Development ◽  
Clinical Samples ◽  
Tyrosine Kinase Receptor ◽  
Cerebellar Granule Neuron ◽  
Cerebellum Development ◽  
The Impact

Medulloblastoma is the most common and malignant pediatric brain tumor in childhood. It originates from dysregulation of cerebellar development, due to an excessive proliferation of cerebellar granule neuron precursor cells (CGNPs). The underlying molecular mechanisms, except for the role of SHH and WNT pathways, remain largely unknown. ERBB4 is a tyrosine kinase receptor whose activity in cancer is tissue dependent. In this study, we characterized the role of ERBB4 during cerebellum development and medulloblastoma progression paying particular interests to its role in CGNPs and medulloblastoma stem cells (MBSCs). Our results show that ERBB4 is expressed in the CGNPs during cerebellum development where it plays a critical role in migration, apoptosis and differentiation. Similarly, it is enriched in the population of MBSCs, where also controls those critical processes, as well as self-renewal and tumor initiation for medulloblastoma progression. These results are translated to clinical samples where high levels of ERBB4 correlate with poor outcome in Group 4 and all medulloblastomas groups. Transcriptomic analysis identified critical processes and pathways altered in cells with knock-down of ERBB4. These results highlight the impact and underlying mechanisms of ERBB4 in critical processes during cerebellum development and medulloblastoma.

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