Craniofacial transitions: the role of EMT and MET during head development

Abstract

Within the developing head, tissues undergo cell-fate transitions to shape the forming structures. This starts with the neural crest, which undergoes epithelial-to-mesenchymal transition (EMT) to form, amongst other tissues, many of the skeletal tissues of the head. In the eye and ear, these neural crest cells then transform back into an epithelium, via mesenchymal-to-epithelial transition (MET), highlighting the flexibility of this population. Elsewhere in the head, the epithelium loses its integrity and transforms into mesenchyme. Here, we review these craniofacial transitions, looking at why they happen, the factors that trigger them, and the cell and molecular changes they involve. We also discuss the consequences of aberrant EMT and MET in the head.

mir152hypomethylation as a mechanism for non-syndromic cleft lip and palate

“…TGFbeta and EMT pathways have been extensively associated with both syndromic and nonsyndromic forms of oral clefting. Indeed, gene pathways associated with NSCLP seem to converge around the process of EMT, either via loss-of-function variants in EMT genes or misregulation of such genes by regulatory polymorphisms, which has been further investigated with animal models [58][59][60][61][62]. It has also been shown that upregulation of mir152 targets DNMT1, which in turn controls CDH1 expression via DNA methylation affecting E-cadherin levels and EMT in breast cancer cells [63,64].…”

Semaphorin‐RhoA signaling regulates HERS maintenance by acting against TGF‐β‐induced EMT

“…As root dentin formation progresses, some HERS cells on the crown side are known to get disrupted and form the epithelial rests of Malassez (ERM); however, the underlying mechanism is controversial. There are two main theories regarding the molecular mechanism, that is, some cells of HERS undergo apoptosis 6 or migrate to the surrounding tissues by epithelial–mesenchymal transition (EMT) 7 . We previously showed that HERS are unique cells with both epithelial and mesenchymal characteristics and are involved in EMT 8,9 .…”

“…There are two main theories regarding the molecular mechanism, that is, some cells of HERS undergo apoptosis 6 or migrate to the surrounding tissues by epithelial-mesenchymal transition (EMT). 7 We previously showed that HERS are unique cells with both epithelial and mesenchymal characteristics and are involved in EMT. 8,9 Additionally, transforming growth factor beta (TGFβ) and fibroblast growth factor 2 (FGF2) have been suggested to induce EMT in HERS cells.…”

Arginine methylation in the epithelial‐to‐mesenchymal transition

“…Observations of intermediate phenotypes suggestive of a hybrid epithelial-mesenchymal status have inspired the notion that biological EMT is not simply a binary switch between epithelial and mesenchymal state, but rather a spectrum of intermediary phases that are biologically flexible (1)(2)(3)(4). The plasticity of the EMT and its reverse process mesenchymal to epithelial transition (MET) is essential for various developmental and pathological processes to achieve transient phenotypic changes (2,(5)(6)(7)(8). EMT is also closely associated with migration and invasion that are critical for cancer metastasis, stemness and apoptosis evasion, which can cause resistance to cancer therapy (2,5,9,10).…”

“…Observations of intermediate phenotypes suggestive of a hybrid epithelial-mesenchymal status have inspired the notion that biological EMT is not simply a binary switch between epithelial and mesenchymal state, but rather a spectrum of intermediary phases that are biologically flexible [1][2][3][4]. The plasticity of the EMT and its reverse process mesenchymal to epithelial transition (MET) is essential for various developmental and pathological processes to achieve transient phenotypic changes [2,5,6,7,8]. EMT is also closely associated with migration and invasion that are critical for cancer metastasis, stemness, Abbreviations ADMA, asymmetric dimethylarginine; CARM1, coactivator associated arginine methyltransferase 1; EMT, epithelial-to-mesenchymal transition; EMT-TF, EMT-specific transcription factor; ESRP, epithelial splicing regulatory protein; FGF, fibroblast growth factors; GSK3b, glycogen synthase kinase-3b; HnRNPA1, heterogeneous nuclear ribonucleoprotein A1; IGF, insulin growth factor; KLF4, Kr€ uppel-like factor 4; LSD1, lysine-specific demethylase 1; MMA, mono-methyl-arginine; NICD, Notch intracellular domain; PRC2, polycomb repressive complex 2; PRMT, protein arginine methyltransferase; RBFOX2, RNA binding fox-1 homolog 2; SAM, S-adenosylmethionine; SDMA, symmetric dimethylarginine; SRSF1, serine-arginine-rich family splicing factor 1; SWI/SNF, switch/sucrose nonfermentable; TGFb, transforming growth factor beta.…”