title: Signalling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis.
abstract: During central nervous system development, neural progenitors are patterned to form discrete neurogenic and non-neurogenic zones. In the zebrafish hindbrain, neurogenesis is organised by Fgf20a emanating from neurons located at each segment centre that inhibits neuronal differentiation in adjacent progenitors. Here, we have identified a molecular mechanism that clusters fgf20a-expressing neurons in segment centres and uncovered a requirement for this positioning in the regulation of neurogenesis. Disruption of hindbrain boundary cell formation alters the organisation of fgf20a-expressing neurons, consistent with a role of chemorepulsion from boundaries. The semaphorins Sema3fb and Sema3gb, which are expressed by boundary cells, and their receptor Nrp2a are required for clustering of fgf20a-expressing neurons at segment centres. The dispersal of fgf20a-expressing neurons that occurs following the disruption of boundaries or of Sema3fb/Sema3gb signalling leads to reduced FGF target gene expression in progenitors and an increased number of differentiating neurons. Sema3 signalling from boundaries thus links hindbrain segmentation to the positioning of fgf20a-expressing neurons that regulates neurogenesis.
authors: Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors: Javier
authors: J
authors: Terriente
authors: Sebastian S
authors: SS
authors: Gerety
authors: Tomomi
authors: T
authors: Watanabe-Asaka
authors: Rosa
authors: R
authors: Gonzalez-Quevedo
authors: David G
authors: DG
authors: Wilkinson
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008959:Models, Neurological; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D039943:Neuropilin-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism; D039961:Semaphorins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D039943:Neuropilin-2; D039961:Semaphorins; D029961:Zebrafish Proteins; C503561:fibroblast growth factor 20, zebrafish; D005346:Fibroblast Growth Factors