The rhombic lip gives rise to neuronal populations that contribute to cerebellar, proprioceptive and interoceptive networks. Cell production depends on the expression of the basic helix-loop-helix (bHLH) transcription factor Atoh1. In rhombomere 1, Atoh1-positive cells give rise to both cerebellar neurons and extra-cerebellar nuclei in ventral hindbrain. The origin of this cellular diversity has previously been attributed to temporal signals rather than spatial patterning. Here, we show that in both chick and mouse the cerebellar Atoh1 precursor pool is partitioned into initially cryptic spatial domains that reflect the activity of two different organisers: an isthmic Atoh1 domain, which gives rise to isthmic nuclei, and the rhombic lip, which generates deep cerebellar nuclei and granule cells. We use a combination of in vitro explant culture, genetic fate mapping and gene overexpression and knockdown to explore the role of isthmic signalling in patterning these domains. We show that an FGF-dependent isthmic Atoh1 domain is the origin of distinct populations of Lhx9-positive neurons in the extra-cerebellar isthmic nuclei. In the cerebellum, ectopic FGF induces proliferation while blockade reduces the length of the cerebellar rhombic lip. FGF signalling is not required for the specification of cerebellar cell types from the rhombic lip and its upregulation inhibits their production. This suggests that although the isthmus regulates the size of the cerebellar anlage, the downregulation of isthmic FGF signals is required for induction of rhombic lip-derived cerebellar neurons.
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http://dx.doi.org/10.1242/dev.099119 | DOI Listing |
Nat Genet
January 2025
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
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Department of Human Anatomy and Cell Science, The Children's Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium.
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Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine University of Southern California, Los Angeles, CA, USA.
Anat Cell Biol
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Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Anterior external arcuate fibers (AEAF) are efferents of the arcuate nuclei, which are located on the ventral surface of pyramids. Several types of fibre bundles superficial to the pyramids have been described in early and mid 20th century. Recently, few of these have been studied in detail.
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Department of Biochemistry and Forensic Sciences, School of Chemistry and Biochemical Science, C. K. Tedam University of Technology and Applied Sciences, P. O. Box 24, Navrongo, Ghana.
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