BMP antagonists and FGF signaling contribute to different domains of the neural plate in Xenopus

Abstract

In ectodermal explants from Xenopus embryos, inhibition of BMP signaling is sufficient for neural induction, leading to the idea that neural fate is the default state in the ectoderm. Many of these experiments assayed the action of BMP antagonists on animal caps, which are relatively naïve explants of prospective ectoderm, and different results have led to debate regarding both the mechanism of neural induction and the appropriateness of animal caps as an assay system. Here we address whether BMP antagonists are only able to induce neural fates in pre-patterned explants, and the extent to which neural induction requires FGF signaling. We suggest that some discrepancies in conclusion depend on the interpretations of sox gene expression, which we show not only marks definitive neural tissue, but also tissue that is not yet committed to neural fates. Part of the early sox2 domain requires FGF signaling, but in the absence of organizer signaling, this domain reverts to epidermal fates. We also reinforce the evidence that ectodermal explants are naïve, and that explants that lack any dorsal prepattern are readily neuralized by BMP antagonists, even when FGF signaling is inhibited.

ERF and ETV3L are retinoic acid-inducible repressors required for primary neurogenesis

“…Primary neurogenesis is preceded by neural induction, which requires inhibition of bone morphogenetic protein (BMP) signaling (Wills et al, 2010;Wilson and Hemmati-Brivanlou, 1995) together with active fibroblast growth factor (FGF) signaling (reviewed by Dorey and Amaya, 2010;Marchal et al, 2009;Wills et al, 2010). Neural induction leads to the expression of proproliferative and neural-fate stabilizing transcription factors such as Foxd4l1, Geminin, Sox2/3 and Zic-family genes (Branney et al, 2009;Marchal et al, 2009;Yan et al, 2009).…”

The RNA-binding protein Xp54nrb isolated from a Ca2+-dependent screen is expressed in neural structures during Xenopus laevis development

“…To verify whether animal caps possess naïve properties in our hands we assayed the expression of Pax3, a marker of neural border character (Wills et al, 2010). As shown on Fig.…”

Role of Signaling Pathways and Epigenetic Factors in Lineage Determination During Human Embryonic Stem Cell Differentiation

“…Inhibition of FGF is required for blood development [48][49][50], whereas activation of FGF signaling is required for neural differentiation [51]. However the mechanism by which FGF aids in embryonic neural differentiation is not fully understood [52][53]. In vitro studies have mimicked the role of FGF signaling in hESC maintenance and differentiation.…”

“…While there are no specific studies which delineate the inductive and maintenance/proliferative roles of FGF during hESC differentiation, work with mESCs have given ambiguous results, some showing that autocrine FGF2 is essential for neural differentiation [57] while others showing that FGF2 has a role in maintenance rather than induction of neural differentiation [58][59]. However, FGF signaling does seem to be necessary for inducing the posterior nervous system in vertebrate embryos [53,60].…”

“…Activin/Nodal [23][24] FGF [24,[38][39][54][55] Block Activin/Nodal [12,14] Low Activin/Nodal [13,[18][19] Short-term BMP [18][19]27] FGF [44][45][46][47], Wnt [66,[68][69]73] High Activin/Nodal [13,17,[20][21] Wnt [66, 68-69, 71, 73] Low PI3K [21,85] Block Activin/Nodal [12,14] High BMP [15] Block Activin/Nodal [12,14,22] Block BMP [15,22] FGF [51,53,57,60] Block Activin/Nodal [12,14] Low BMP [16], FGF [51,57] Hippo [101] (? )…”