FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9.
The mechanisms underlying the generation of neural cell diversity are the subject of intense investigation, which has highlighted the involvement of different signalling molecules including Shh, BMP and Wnt. By contrast, relatively little is known about FGF in this process. In this report we identify an FGF-receptor-dependent pathway in zebrafish hindbrain neural progenitors that give rise to somatic motoneurons, oligodendrocyte progenitors and differentiating astroglia. Using a combination of chemical and genetic approaches to conditionally inactivate FGF-receptor signalling, we investigate the role of this pathway. We show that FGF-receptor signalling is not essential for the survival or maintenance of hindbrain neural progenitors but controls their fate by coordinately regulating key transcription factors. First, by cooperating with Shh, FGF-receptor signalling controls the expression of olig2, a patterning gene essential for the specification of somatic motoneurons and oligodendrocytes. Second, FGF-receptor signalling controls the development of both oligodendrocyte progenitors and astroglia through the regulation of sox9, a gliogenic transcription factor the function of which we show to be conserved in the zebrafish hindbrain. Overall, for the first time in vivo, our results reveal a mechanism of FGF in the control of neural cell diversity.
Esain
Virginie
V
INSERM, U784, Laboratoire de Génétique Moléculaire du Développement, 46 rue d'Ulm, 75230 Paris Cedex 05, France.
Postlethwait
John H
JH
Charnay
Patrick
P
Ghislain
Julien
J
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D012249:Rhombencephalon / Q000166:cytology* / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D017468:Receptors, Fibroblast Growth Factor; D055758:SOX9 Transcription Factor; D029961:Zebrafish Proteins; C504918:Sox9a protein, zebrafish; C504919:Sox9b protein, zebrafish; C465361:olig2 protein, zebrafish