Inhibition of BMP Activity by the FGF Signal Promotes Posterior Neural Development in Zebrafish

Abstract

The expression patterns of region-specific neuroectodermal genes and fate-map analyses in zebrafish gastrulae suggest that posterior neural development is initiated by nonaxial signals, distinct from organizer-derived secreted bone morphogenetic protein (BMP) antagonists. This notion is further supported by the misexpression of a constitutively active form of zebrafish BMP type IA receptor (CA-BRIA) in the zebrafish embryos. It effectively suppressed the anterior neural marker, otx2, but not the posterior marker, hoxb1b. Furthermore, we demonstrated that the cells in the presumptive posterior neural region lose their neural fate only when CA-BRIA and Xenopus dominant-negative fibroblast growth factor (FGF) receptors (XFD) are coexpressed. The indications are that FGF signaling is involved in the formation of the posterior neural region, counteracting the BMP signaling pathway within the target cells. We then examined the functions of Fgf3 in posterior neural development. Zebrafish fgf3 is expressed in the correct place (dorsolateral margin) and at the correct time (late blastula to early gastrula stages), the same point that the most precocious posterior neural marker, hoxb1b, is first activated. Unlike other members of the FGF family, Fgf3 had little mesoderm-inducing activity. When ectopically expressed, Fgf3 expands the neural region with suppression of anterior neural fate. However, this effect was mediated by Chordino (zebrafish Chordin), because Fgf3 induces chordino expression in the epiblast and Fgf3-induced neural expansion was substantially suppressed in dino mutants with mutated chordino genes. The results obtained in the present study reveal multiple actions of the FGF signal on neural development: it antagonizes BMP signaling within posterior neural cells, induces the expression of secreted BMP antagonists, and suppresses anterior neural fate.

FGF signaling in gastrulation and neural development in Nematostella vectensis, an anthozoan cnidarian

“…It has recently been shown that the pharynx of cnidarians asymmetrically expresses several of the genes found in the vertebrate "organizer", including TGF-β antagonists NvNoggin1 and NvFollistatin and a transcription factor NvGsc (Matus et al 2006a), and that some of these genes are also expressed at the aboral pole at the base of the apical tuft, a chemosensory structure . FGF signaling alone in ascidians (Bertrand et al 2003;Miya and Nishida 2003) or together with TGF-β antagonism in vertebrates (De Robertis and Kuroda 2004;Delaune et al 2005;Koshida et al 2002) coordinate neural induction. It seems likely then that the expression of FGF signaling pathway genes in the pharynx and apical tuft may to be playing a role in neural induction in N. vectensis.…”

Transient, afferent input-dependent, postnatal niche for neural progenitor cells in the cochlear nucleus

“…In this respect, it is important to note that the growth medium used contains EGF, IGF1, and basic FGF as part of a commonly used mixture of factors that promote neurosphere formation (21,35). Particularly, interplay between FGF-induced suppression of BMPs, which often antagonize during embryonic development (36,37), might play a role in promoting neurosphere formation from CN cells. This hypothesis is supported by our observation that inhibition of FGF signaling virtually abolished neurosphere formation.…”

Sp5l is a mediator of Fgf signals in anteroposterior patterning of the neuroectoderm in zebrafish embryo

“…Compared to wildtype and fgf17b-injected embryos, some of affected embryos that were coinjected with fgf17 mRNA and sp5l-MO showed weaker expression though the expression domain still shifted anteriorly and expanded ventrally. rior neuroectodermal fate upon overexpression in zebrafish embryos (Koshida et al, 2002;Kudoh et al, 2002;Cao et al, 2004;Rentzsch et al, 2004). We re-investigated effects of Fgf signaling on the anteroposterior neuroectodermal patterning by overexpressing fgf17b, which has a strong neuroectodermal posteriorizing activity (Cao et al, 2004).…”

“…These data further support the notion that sp5l plays a role in mediating Fgf activity in the anteroposterior patterning of the neuroectoderm. sp5l is Required for fgf8 and fgf3 Expression in the Hindbrain During Gastrulation fgf3 and fgf8 are expressed in the forebrain and hindbrain during and after gastrulation in zebrafish embryos (Reifers et al, 1998;Phillips et al, 2001), and they play important roles in the formation and patterning of the forebrain and hindbrain (Reifers et al, 1998;Shinya et al, 2001;Koshida et al, 2002;Maves et al, 2002;Walshe et al, 2002;Walshe and Mason, 2003). Given that sp5l is expressed in the posterior neuroectoderm during gastrulation (Zhao et al, 2003), we asked whether it is required for expression of fgf3 and fgf8 in the hindbrain.…”

“…In Xenopus, application of exogenous bFgf to the ectodermal explants induces the posterior neural fates (Cox and Hemmati-Brivanlou, 1995;Kengaku and Okamoto, 1995;Lamb and Harland, 1995), whereas blockade of Fgf signaling with a dominant negative Fgf receptor (XFD) or dominant negative Ras mutant inhibits expression of some posterior neural markers (Holowacz and Sokol, 1999;Ribisi et al, 2000). Similarly, overexpression of Fgf molecules in zebrafish embryos promotes posterior neural fates, which is accompanied by inhibition of anterior neural development (Koshida et al, 2002;Kudoh et al, 2002;Cao et al, 2004;Rentzsch et al, 2004). However, few transcription factors have been proved to be mediators of Fgf signals in neuroectodermal posteriorization.…”