Intracellular Communication among Morphogen Signaling Pathways during Vertebrate Body Plan Formation.

Kimiko Takebayashi-Suzuki,Atsushi Suzuki

doi:10.3390/genes11030341

Abstract

During embryonic development in vertebrates, morphogens play an important role in cell fate determination and morphogenesis. Bone morphogenetic proteins (BMPs) belonging to the transforming growth factor-β (TGF-β) family control the dorsal–ventral (DV) patterning of embryos, whereas other morphogens such as fibroblast growth factor (FGF), Wnt family members, and retinoic acid (RA) regulate the formation of the anterior–posterior (AP) axis. Activation of morphogen signaling results in changes in the expression of target genes including transcription factors that direct cell fate along the body axes. To ensure the correct establishment of the body plan, the processes of DV and AP axis formation must be linked and coordinately regulated by a fine-tuning of morphogen signaling. In this review, we focus on the interplay of various intracellular regulatory mechanisms and discuss how communication among morphogen signaling pathways modulates body axis formation in vertebrate embryos.

Highlights

A morphogen is defined as a molecule released from a localized source that determines several different cell fates and controls morphogenesis by regulating gene expression in a concentration-dependent manner [1,2]
Well-known morphogens are bone morphogenetic proteins (BMPs), Nodals, and Activins, which all belong to the transforming growth factor-β (TGF-β) family, fibroblast growth factors (FGFs), and Wnt family proteins [3,4,5,6,7,8,9,10,11,12,13,14,15]
These findings suggest that Cdc2-like kinase 2 (Clk2) is involved in the establishment of the DV and AP axes via modulation of the BMP and FGF signaling pathways

Summary

Introduction

A morphogen is defined as a molecule released from a localized source that determines several different cell fates and controls morphogenesis by regulating gene expression in a concentration-dependent manner [1,2]. Most morphogens are secreted molecules that bind to transmembrane receptors, activate intracellular signal transducers, and regulate the expression of downstream target genes. Anterior-posterior patterning of embryos regulated by FGF, Wnt, and signaling mitogen-activated (MAPK) is pathway consisting of MAPKKKs Wnt/β-Catenin signaling induces the expression of the homeobox genes cad and meis that are important for posterior development [53,54]. It has been shown that FGF, Wnt, and RA signaling cascades function in concert to regulate gene expression along the AP axis of the embryo [12,59,60,61,62,63]. In the following parts of this review, we discuss how communication among morphogen signaling pathways, especially BMP, FGF, Wnt, and RA signaling, is achieved intracellularly and functions as the molecular link that coordinates DV and AP patterning during body plan formation in vertebrates

Phosphorylation of Smad

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Conclusion and Perspectives