Neuronal regulation of the spatial patterning of neurogenesis.
Precise regulation of neurogenesis is achieved in specific regions of the vertebrate nervous system by formation of distinct neurogenic and nonneurogenic zones. We have investigated how neurogenesis becomes confined to zones adjacent to rhombomere boundaries in the zebrafish hindbrain. The nonneurogenic zone at segment centers comprises a distinct progenitor population that expresses fibroblast growth factor (fgfr) 2, erm, sox9b, and the retinoic acid degrading enzyme, cyp26b1. FGF receptor activation upregulates expression of these genes and inhibits neurogenesis in segment centers. Cyp26 activity is a key effector inhibiting neuronal differentiation, suggesting antagonistic interactions with retinoid signaling. We identify the critical FGF ligand, fgf20a, which is expressed by specific neurons located in the mantle region at the center of segments, adjacent to the nonneurogenic zone. Fgf20a mutants have ectopic neurogenesis and lack the segment center progenitor population. Our findings reveal how signaling from neurons induces formation of a nonneurogenic zone of neural progenitors.
Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Rosa
R
Gonzalez-Quevedo
Yoonsung
Y
Lee
Kenneth D
KD
Poss
David G
DG
Wilkinson
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000072516:Retinoic Acid 4-Hydroxylase; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D055758:SOX9 Transcription Factor; C504919:Sox9b protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; C513244:etv5b protein, zebrafish; C503561:fibroblast growth factor 20, zebrafish; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; C502199:cyp26b1 protein, zebrafish