FGF-receptor signalling controls neural cell diversity in the zebrafish hindbrain by regulating olig2 and sox9

Abstract

SUMMARYThe 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.

A Sox9/Fgf feed-forward loop maintains pancreatic organ identity

“…For example, Fgf receptor-transduced signaling promotes Sox9 expression in embryonic zebrafish hindbrain (Esain et al, 2010) and mouse chondrocytes (Murakami et al, 2000), and Fgfr2 ablation diminishes Sox9 expression in both developing testes (Bagheri-Fam et al, 2008) and lung (Abler et al, 2009). Our findings now pave the way for future studies addressing whether Sox9, Fgfr2b and Fgf10 also operate in a feed-forward loop in other tissues and organs, and whether this loop acts as a paradigm for integrating cell-extrinsic and -intrinsic cues to expand progenitors and reinforce their fate commitment in multiple developmental and regenerative contexts.…”

Development of hypothalamic serotoninergic neurons requires Fgf signalling via the ETS-domain transcription factor Etv5b

“…The Tg(ermp:gv) transgenic line expressing Gal4:VP16 under the control of etv5b regulatory elements (Esain et al, 2010) (kindly provided by Julien Ghislain) intercrossed with the Tg(uas:gfp) (Scheer et al, 2001) line was used for lineage-tracing experiments. For cell cycle experiments, embryos from an intercross of the Tg(EF1:mKO2-zCdt1) and Tg(EF1:mAG-hGem) lines (Sakaue-Sawano et al, 2008) based on the Fucci technique (Sugiyama et al, 2009) were used.…”

“…5-HT clusters and analysed whether these neurons originate from cells expressing etv5b. etv5b expression is strongest before 5-HT is detectable, and as we were unsuccessful at performing 5-HT immunohistochemistry after ISH, we took advantage of the ermp:gv and uas:gfp transgenic lines (Esain et al, 2010;Scheer et al, 2001). Transcripts for gfp and etv5b colocalised at 30, 36 and 40 hpf in the hypothalamus ( Fig (Fig.…”

Signalling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis

“…In fgf20a mutant embryos, ectopic neurogenesis occurs throughout segment centres, probably owing to a lack of inhibition of neuronal differentiation rather than to altered proliferation of a progenitor population, as FGF signalling does not affect hindbrain cell proliferation at these stages (Gonzalez-Quevedo et al, 2010). Concurrent with the inhibition of neurogenesis, FGF signalling may promote gliogenesis in segment centres (Esain et al, 2010) and thus underlie a switch in cell fate. These findings suggest that it is the localisation of fgf20a expression to form a signalling centre in the mantle zone that underlies the stereotyped patterning of neurogenesis.…”