Neural Induction in Whole Chick Embryo Cultures by FGF

Abstract

FGFs are well known as mesodermal inducers and they have been reported to have neural inducing and/or caudalizing activity in Xenopus. To evaluate the role of FGFs in neural induction and patterning of the nervous system in chick embryos, we have targeted the ectopic expression of these factors by applying FGF-soaked beads to extended primitive streak chick embryos developing in culture. The whole embryo culture system allows to directly assessing the neural inducing activity on nonneural ectodermal cells. Our results show that FGFs induce the production of ectopic neural structures in the epiblast cell layer which are independent of the endogenous neural tube. The induced neural plates express several neural positional markers (Otx-2, Krox-20, EphA4, EphA7, and cHox-B9), although they lack anterior neural markers such as BF-1. These effects are very likely to be exerted by the direct action of FGF on epiblast cells because we have found no evidence of the induction of an organizer-like activity or of the presence of new axial mesoderm induced by the growth factor. We conclude that FGFs can act as direct neural inducers and that this action is exerted independently from the axial mesoderm.

Neural induction: old problem, new findings, yet more questions

“…In vertebrates, there has been more controversy about the role of FGFs in neural induction. It has been claimed that FGFs can direct ectodermal cells to a neural pathway in amphibians (Kengaku and Okamoto, 1995;Lamb and Harland, 1995;Hongo et al, 1999;Strong et al, 2000), zebrafish (Kudoh et al, 2004) and chick (Rodríguez-Gallardo et al, 1997;Alvarez et al, 1998;Storey et al, 1998) in the absence of other signals. However, in Xenopus, this activity requires special experimental conditions (either partial dissociation of the cells or the isolation of animal caps) (Pera et al, 2003;Linker and Stern, 2004;Delaune et al, 2005), while in chick, the induced neural tissue is of a posterior character; whether or not the induction is direct (without the prior induction of mesoderm and/or endoderm) has not been firmly established.…”

Involvement of BMP‐4/msx‐1 and FGF pathways in neural induction in the Xenopus embryo

“…Two research groups have demonstrated that FGF is a potent neural inducer (Kengaku & Okamoto 1993, 1995Lamb & Harland 1995). Furthermore, in the chicken embryo, it has been shown that FGF can induce posterior neural tissues from epiblasts (Alvarez et al 1998;Storey et al 1998 (Maeda et al 1997;Suzuki et al 1997;Takeda et al 2000. The expression pattern in the gastrula embryo suggested that Xmsx-1 functions in an earlier step of neural tissue formation than that indicated by a previous study (Su et al 1991) …”

“…All BMP-4 antagonizers, such as noggin, follistatin, chordin, and cerberus, exclusively induced the anterior neural markers (Lamb et al 1993;Sasai et al 1995;Bouwmeester et al 1996) (Sokol 1996;Blumberg et al 1997;Holowacz & Sokol 1999 (Kengaku & Okamoto 1993, 1995Lamb & Harland 1995), whereas recent studies have shown that FGF is not essential for the primary induction of neural cells but for the transformation step from anterior to posterior type (Cox & Hemmati-Brivanlou 1995;Godsave & Durston 1997;Holowacz & Sokol 1999 (Kroll & Amaya 1996). Recent studies on chicken embryos provided evidence for both direct and indirect actions of FGF on prospective posterior neural tissues (Alvarez et al 1998;Storey et al 1998). Also, an analysis of a new member of FGF in zebrafish suggested that FGF-3 directly induced a posterior neural marker in presumptive ectodermal cells, and that it cross-talked the BMP-4 signal to block it (H. Takeda et al, pers.…”

A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways

“…Taken together, these previous publications and the data presented here indicate that the same signalling molecule can be involved in induction and cell migration at different times during development. Although early findings implicating FGF in neural induction (Lamb and Harland, 1995;Alvarez et al, 1998;Hongo et al, 1999) were controversial, the evidence is now strong that FGF is indeed involved in the induction of neural tissue (Sasai et al, 1994;Smith et al, 1993;Launay et al, 1996;Linker and Stern, 2004;Pera et al, 2003;Streit et al, 1998;Streit et al, 2000;Wilson et al, 2000). Moreover, FGF contributes to the inhibition of BMP signalling, at least in part by phosphorylation of Smad1 during neural induction (Fuentealba et al, 2007;Kuroda et al, 2005).…”