FGF Is Required for Posterior Neural Patterning but Not for Neural Induction

Abstract

Fibroblast growth factor (FGF) has been implicated in a variety of developmental processes including posterior mesoderm and neural patterning. Previous work has led to contradictory roles for FGF in neural induction and anteroposterior neural patterning. Launay et al. (Development 122, 869-880, 1996) suggested a requirement for FGF in anterior neural induction. In contrast, Kroll and Amaya (Development 122, 3173-3183, 1996) and Bang et al. (Development 124, 2075-2085, 1997) proposed that FGF is not required for early neural patterning. Here we use a loss-of-function assay to examine whether FGF is required for neural patterning in three experimental situations: (i) in Xenopus early embryos, (ii) in embryonic explants consisting of presumptive dorsal mesoderm and neurectoderm (Keller explants), and (iii) in explants of dorsal ectoderm and posterior mesoderm in which FGF signaling is specifically blocked in the ectoderm. When cultured until tailbud stages, Keller explants develop neural tissue with normal anteroposterior pattern. Overexpression of the dominant-negative FGF receptor (XFD) in Keller explants inhibited the posterior neural markers En-2, Krox-20, and HoxB9, but not the panneural marker nrp-1 and the anterior neurectodermal markers XAG-1 and Xotx-2. Similar results were seen in whole embryos, but only when XFD RNA was targeted to both the dorsal and lateral regions. In contrast, addition of FGF to Keller explants resulted in a shift of the midbrain-hindbrain boundary marker En-2 to a more anterior position normally fated to become cement gland. We also determined whether FGF is required specifically by the neurectoderm for anteroposterior neural patterning. Recombinants of dorsal ectoderm and posterior mesoderm were made in which FGF was specifically blocked in the ectoderm. Spinal cord and hindbrain markers were inhibited in these recombinants, whereas anterior markers and cement gland development were enhanced. Our results demonstrate that FGF is important for posterior development in both mesoderm and neurectoderm and that neural induction and posteriorization represent separable developmental events.

Wnt Signaling in Vertebrate Axis Specification

“…Organizer-derived posteriorizing signals reach neuroectoderm during gastrulation to specify the anteroposterior axis (Nieuwkoop 1952;Doniach et al 1992;Holowacz and Sokol 1999). Besides Wnt signaling, this process requires additional pathways, such as BMP and FGF signaling.…”

“…In contrast to the BMP pathway that is active in the ventral region of the blastula embryo, FGF signaling seems to be essential for dorsal posterior patterning (Amaya et al 1991;Cox and Hemmati-Brivanlou 1995;Lamb and Harland 1995;Holowacz and Sokol 1999;Schohl and Fagotto 2002;Kudoh et al 2004;Marchal et al 2009;Martin and Kimelman 2009). Many Wntinducible genes, including Cdx4, Xpo, Meis, and Marginal coil (Xmc), have been previously identified as FGF-responsive genes (Table 1) (Amaya et al 1993;Frazzetto et al 2002;Aamar and Frank 2004;Chung et al 2004;Keenan et al 2006).…”

Morphogen gradients, positional information, and Xenopus: Interplay of theory and experiment

“…FGF does seem to be able to diffuse over several cell diameters (Christen and Slack, 1999), and it has been proposed to be a morphogen in early posterior patterning of the nervous system in Xenopus: embryonic FGF (eFGF) may act during gastrulation stages to induce expression of posterior Hox genes and posterior neural markers (Xu et al, 1997;Isaacs et al, 1998;Pownall et al, 1998;Holowacz and Sokol, 1999). However, more detailed analysis of FGF's potential morphogen activity is difficult because the rapid increase in anatomic complexity makes quantitation problematic.…”

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

“…When the animal cap was treated with bFGF and BMP-antagonists, for example, noggin, the posterior neural tissues were differentiated in addition to the anterior tissues (Cox & Hemmati-Brivanlou 1995). An approach utilizing a dominant-negative form of the FGF receptor (XFD) showed that FGF signaling is essential for the posterior central nervous system (Holowacz & Sokol 1999). Although there has been accumulating evidence supporting the 'two step model', the existence of direct trunk neural inducers cannot be ruled out.…”