Abstract

Early embryonic development is a multi-step process that is intensively regulated by various signaling pathways. Because of the complexity of the embryo and the interactions between the germ layers, it is very difficult to fully understand how these signals regulate embryo patterning. Recently, pluripotent stem cell lines derived from different developmental stages have provided an in vitro system for investigating molecular mechanisms regulating cell fate decisions. In this review, we summarize the major functions of the BMP, FGF, Nodal and Wnt signaling pathways, which have well-established roles in vertebrate embryogenesis. Then, we highlight recent studies in pluripotent stem cells that have revealed the stage-specific roles of BMP,FGF and Nodal pathways during neural differentiation. These findings enhance our understanding of the stepwise regulation of embryo patterning by particular signaling pathways and provide new insight into the mechanisms underlying early embryonic development.

Highlights

  • Embryogenesis is a process by which the zygote develops into a complex and organized embryo.During early development in the mouse, the zygote first develops into a blastocyst containing the innerGenes 2011, 2 cell mass (ICM) inside the trophectoderm

  • We briefly summarize the key functions of the bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), Nodal and Wnt signaling pathways in early embryogenesis, and we discuss recent findings obtained from studies in embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs) that reveal the stage-specific functions of BMP, FGF and Nodal signals

  • We have recently identified ectoderm-like cells that form during mouse EpiSC neural and epidermal differentiation [37], and the signaling pathways involved in ectodermal cell commitment and neural differentiation are currently being investigated

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Summary

Introduction

Embryogenesis is a process by which the zygote develops into a complex and organized embryo. Mechanistic studies require an amenable system with embryonic properties but with the absence of the complexity that exists in vivo Under these circumstances, pluripotent stem cells derived from different developmental stages have become an in vitro system for investigating the detailed molecular mechanisms through which signaling pathways regulate cell fate decisions. ESCs differentiate into derivatives of all three germ layers, and the differentiation of specific cell types from ESCs is directed by a set of signals similar to that which regulates embryonic development in vivo [8,9,10,11] Another type of pluripotent stem cell, referred to as epiblast stem cells (EpiSCs), was derived from the late epiblast tissue of E5.5 mouse embryos. These findings begin to elucidate the mechanisms underlying different stages of early embryonic development

BMP Signaling
FGF Signaling
Nodal Signaling
Wnt Signaling
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