Resolving the mechanisms underlying epithelial‐to‐mesenchymal transition of the lateral plate mesoderm

Abstract

SummaryFormation of the vertebrate limb buds begins with a localized epithelial‐to‐mesenchymal transition (EMT) of the somatic lateral plate mesoderm (LPM). While the processes that drive proliferation and outgrowth of the limb mesenchyme are well established, the fundamental mechanisms that precede this process and initiate EMT are less understood. In this review, we outline putative drivers of EMT of the LPM, drawing from analyses across a range of vertebrates and developmental models. We detail the expression patterns of key EMT transcriptional regulators in the somatic LPM of the presumptive limb fields, and their potential role in producing a mesenchymal cell fate. These include a putative cooperative role between the EMT inducers PRRX1 and TWIST1, supported by evidence in zebrafish and chicken models but unconfirmed data from mice. As such, additional functional data are required to definitively determine the mechanisms that initiate and drive EMT of the somatic LPM, a critical transition preceding formation of the limb bud mesenchyme.

Heterotopic reduction of forelimb progenitors underpins development of the vestigial emu wing; implications for vertebrate limb evolution

“…BMP signals from the overlying ectoderm specify somatic LPM progenitors towards a limb fate, observed by expression of PRRX1, IRX3 and TWIST1 11,16,17 . Epithelial cells in the somatic LPM monolayer then undergo EMT to produce the limb bud mesenchyme 16,18,19 , which in the forelimb, is dependent on the limb initiation factor TBX5 14,[20][21][22][23] . TBX5 activates FGF10 in the limb bud mesenchyme, which establishes a positive feedback loop with FGF8 in the overlying ectoderm to stimulate outgrowth of the limb buds 21,[24][25][26] .…”