DORSAL-VENTRAL PATTERNING AND NEURAL INDUCTION IN XENOPUS EMBRYOS

Abstract

We review the current status of research in dorsal-ventral (D-V) patterning in vertebrates. Emphasis is placed on recent work on Xenopus, which provides a paradigm for vertebrate development based on a rich heritage of experimental embryology. D-V patterning starts much earlier than previously thought, under the influence of a dorsal nuclear β-Catenin signal. At mid-blastula two signaling centers are present on the dorsal side: The prospective neuroectoderm expresses bone morphogenetic protein (BMP) antagonists, and the future dorsal endoderm secretes Nodal-related mesoderminducing factors. When dorsal mesoderm is formed at gastrula, a cocktail of growth factor antagonists is secreted by the Spemann organizer and further patterns the embryo. A ventral gastrula signaling center opposes the actions of the dorsal organizer, and another set of secreted antagonists is produced ventrally under the control of BMP4. The early dorsal β-Catenin signal inhibits BMP expression at the transcriptional level and promotes expression of secreted BMP antagonists in the prospective central nervous system (CNS). In the absence of mesoderm, expression of Chordin and Noggin in ectoderm is required for anterior CNS formation. FGF (fibroblast growth factor) and IGF (insulinlike growth factor) signals are also potent neural inducers. Neural induction by anti-BMPs such as Chordin requires mitogen-activated protein kinase (MAPK) activation mediated by FGF and IGF. These multiple signals can be integrated at the level of Smad1. Phosphorylation by BMP receptor stimulates Smad1 transcriptional activity, whereas phosphorylation by MAPK has the opposite effect. Neural tissue is formed only at very low levels of activity of BMP-transducing Smads, which require the combination of both low BMP levels and high MAPK signals. Many of the molecular players that regulate D-V patterning via regulation of BMP signaling have been conserved between Drosophila and the vertebrates.

Function and biological roles of the Dickkopf family of Wnt modulators

“…One of the functions of Spemann's organizer in Xenopus, the zebrafish shield and the mouse anterior mesendoderm is to antagonize Wnt signals, which together with bone morphogenetic proteins (BMPs) and Nodals, are inhibitory to anterior development in general, and in particular to the anterior central nervous system (De Robertis and Kuroda, 2004;Niehrs, 2004b). The different expression domains of these growth factors and their antagonists, such as Dkk1, create signaling gradients, which pattern the early embryo in a combinatorial fashion and orchestrate regionally specific induction of axial structures, including the head.…”

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

“…In C. elegans, FGF signaling affects axon outgrowth via egl-15 (Bulow et al 2004). In deuterostomes, FGF signaling has been implicated in neural induction in ascidians and all vertebrate models tested thus far (Bertrand et al 2003;Darras and Nishida 2001;De Robertis and Kuroda 2004;Imai et al 2002). Although no data exists on FGF ligand expression in the Lophotrochozoa, FGFRs have, however, been implicated in a role in neurogenesis of the platyhelminth Dugesia japonica (Cebria et al 2002;Mineta et al 2003), suggesting that a conserved role for FGF signaling in neural induction at least extends to the Lophotrochozoa.…”

“…FGF signals often work in concert with other important pathways, such as transforming growth factor-β (TGF-β), Wnt, Hedgehog, and Notch (Gerhart 1999). In both invertebrates and vertebrates, FGF signaling functions in body plan patterning, including mesoderm and neural induction and coordinate cell movements during gastrulation (Bertrand et al 2003;De Robertis and Kuroda 2004;Isaacs et al 1994;Popovici et al 2005;Rossant et al 1997;Sheng et al 2003;Sivak et al 2005;Stathopoulos et al 2004). …”

Ca2+ coding and decoding strategies for the specification of neural and renal precursor cells during development

“…During gastrulation in vertebrates, the ectodermal This is the Pre-Published Version cells give rise to epidermal progenitors on the ventral side of the embryo and to neural progenitors in the dorsal side. This binary choice of cell fate during neural induction is controlled by complex mechanisms that involve both positive effectors (such as fibroblast growth factors, FGFs) and negative effectors (such as bone morphogenetic proteins, BMPs; Wingless/Int proteins, Wnts and Nodal) [4][5][6]. One of the key regulatory mechanisms involved in the conversion of ectoderm into neuroectoderm is the inhibition of the BMP pathway by noggin, chordin, and follistatin, which are factors secreted by the dorsal mesoderm.…”