Early Development of the Central and Peripheral Nervous Systems Is Coordinated by Wnt and BMP Signals

Cédric Patthey,Thomas Edlund,Lena Gunhaga,Lin Mei

doi:10.1371/journal.pone.0001625

Abstract

The formation of functional neural circuits that process sensory information requires coordinated development of the central and peripheral nervous systems derived from neural plate and neural plate border cells, respectively. Neural plate, neural crest and rostral placodal cells are all specified at the late gastrula stage. How the early development of the central and peripheral nervous systems are coordinated remains, however, poorly understood. Previous results have provided evidence that at the late gastrula stage, graded Wnt signals impose rostrocaudal character on neural plate cells, and Bone Morphogenetic Protein (BMP) signals specify olfactory and lens placodal cells at rostral forebrain levels. By using in vitro assays of neural crest and placodal cell differentiation, we now provide evidence that Wnt signals impose caudal character on neural plate border cells at the late gastrula stage, and that under these conditions, BMP signals induce neural crest instead of rostral placodal cells. We also provide evidence that both caudal neural and caudal neural plate border cells become independent of further exposure to Wnt signals at the head fold stage. Thus, the status of Wnt signaling in ectodermal cells at the late gastrula stage regulates the rostrocaudal patterning of both neural plate and neural plate border, providing a coordinated spatial and temporal control of the early development of the central and peripheral nervous systems.

Highlights

Information from our surroundings is transmitted by specific sensory neurons in the peripheral nervous system to the central nervous system were it is processed
The specification of both neural crest and placodal cells is ongoing at the late gastrula stage [4,5], and around this stage, Bmp2 and Bmp4 are expressed in the ectoderm surrounding the entire neural plate [6], domains where phosphorylated Smad-1 is detected, indicative of active Bone Morphogenetic Protein (BMP) signaling [7]
We provide evidence that at the late gastrula stage, Wnt signals impose caudal character on neural plate border cells and that under these conditions, BMP signals induce neural crest cells instead of rostral placodal cells

Summary

Introduction

Information from our surroundings is transmitted by specific sensory neurons in the peripheral nervous system to the central nervous system were it is processed. In development secreted signals specify various cell types of both the central and peripheral nervous systems, which later will establish complex neural circuits that process sensory information. Studies conducted later in development, at neural fold stages, when border cells have started to express neural crest markers [8,9] suggest that both BMP and Wnt signals induce neural crest character in caudal neural cells [10,11,12]. Since neural crest generation has already been initiated at neural fold stages, these results may reflect mechanisms of regeneration and maintenance of inducing capacity rather than the mechanism by which neural crest cells are initially induced It remains unclear whether BMP and Wnt signals act in parallel or have separated roles during the initial induction of neural crest cells

Methods

Results

Conclusion