Neural plate patterning by secreted signals

Abstract

The patterning of the CNS relies on the interaction of multiple signaling molecules such as Sonic Hedgehog, Wnts, and BMPs and their antagonists Chordin and Noggin. The identification of the secreted molecule Tiarin (Tsuda et al., 2002, this issue of Neuron), produced by the nonneural ectoderm at border of the anterior and lateral neural plate, now introduces a novel signaling pathway participating in CNS development.

Figure 1. Patterning of the Neural Plate by Secreted Signals

(A) Schematic representation of a cross-section of a Xenopus early neurula at the time Tiarin is expressed. In the ectodermal germ layer the nonneural ectoderm is shown in red, the neural plate in blue, and the floor plate in orange. Note that at the neural plate stage the dorsal region of the closed neural tube corresponds to the lateral regions, and that the future ventral neural tube corresponds to the medial neural plate. The mesoderm (yellow) is subdivided into four independent regions: the notochord, the somite giving rise mostly to muscle, the intermediate mesoderm giving rise to kidney, and the lateral plate mesoderm, which will give rise to the somatic and visceral mesodermal sheets once the coelomic cavity forms. The endodermal germ layer is shown in green and the hypochord, its dorsal-most derivative, is indicated. (B) The dorsoventral polarity of the future neural tube is established via the interaction of multiple signaling pathways. The floor plate secretes Shh and the notochord Shh and the BMP antagonists Chordin, Noggin, and Follistatin. The activity of these midline signals is opposed by factors secreted by the dorsal most nonneural ectoderm. Wnts, BMPs, and the newly identified Tiarin lead to the formation of dorsal cell types in the neural tube.

Figure 2. Hypothetical Model for the Function of OLF Domain Containing Proteins

(A) Wnt receptor Frizzled and the family of secreted Wnt antagonists of the Frzb/sFRP class contain a CRD domain that binds Wnt. In the case of the receptor, interaction with the Wnt ligand leads to the activation of the seven-transmembrane receptor. In the case of the Frzb/sFRP, Wnt binding removes the ligand from the signaling pool and antagonizes Wnt signaling (after Leyns et al., 1997). (B) Tiarin and the α-Latrotoxin receptor share a common protein domain. Although the molecular mechanism of action of Tiarin is unresolved, the presence of the olfactomedin-like domain (OLF) in Tiarin and in the extracellular region of the receptor is suggestive. The natural endogenous ligand of the α-Latrotoxin receptor is unknown, and the OLF domain could be involved in signaling by either binding a putative ligand or by interacting with extracellular matrix components.