Transforming growth factor β (TGFβ) signalling in palatal growth, apoptosis and epithelial mesenchymal transformation (EMT)

A. Nawshad, D. Lagamba, E. D. Hay

Research output: Contribution to journalReview article

132 Citations (Scopus)

Abstract

Formation of the medial edge epithelial (MEE) seam by fusing the palatal shelves is a crucial step of palate development. The opposing shelves adhere to each other at first by adherens junctions, then by desmosomes in the MEE. The MEE seam disappears by epithelial mesenchymal transformation (EMT), which creates confluence of connective tissue across the palate. Cleft palate has a mutifactorial etiology that often includes failure of adherence of apposing individual palatal shelves and/or EMT of the MEE. In this review, we first discuss TGFβTGFβ refers to both the human and murine growth factor in this review.# biology, including functions of TGFβ isoforms, receptors, down stream transcription factors, endosomes, and signalling pathways. Different isoforms of the TGFβ family play important roles in regulating various aspects of palate development. TGFβ1 and TGFβ2 are involved in growth, but it is TGFβ3 that regulates MEE transformation to mesenchyme to bring about palatal confluence. Its absence results in cleft palate. Understanding of TGFβ family signalling is thus essential for development of therapeutic strategies. Because TGFβ3 and its downstream target, LEF1, play the major role in epithelial transformation, it is important to identify the signalling pathways they use for palatal EMT. Here, we will discuss in detail the mechanisms of palatal seam disappearance in response to TGFβ3 signalling, including the roles, if any, of growth and apoptosis, as well as EMT in successful MEE adherence and seam formation. We also review recent evidence that TGFβ3 uses Smad2 and 4 during palatal EMT, rather than β-Catenin, to activate LEF1. TGFβ1 has been reported to use non-Smad signalling using RhoA or MAPKinases in vitro, but these are not involved in activation of palatal EMT in situ. A major aim of this review is to document the genetic mechanisms that TGFβ uses to bring about palatal EMT and to compare these with EMT mechanisms used elsewhere.

Original languageEnglish (US)
Pages (from-to)675-689
Number of pages15
JournalArchives of Oral Biology
Volume49
Issue number9
DOIs
StatePublished - Sep 1 2004

Fingerprint

Epithelial-Mesenchymal Transition
Transforming Growth Factors
Apoptosis
Growth
Palate
Cleft Palate
Protein Isoforms
Adherens Junctions
Catenins
Desmosomes
Growth Factor Receptors
Endosomes
Mesoderm
Connective Tissue
Intercellular Signaling Peptides and Proteins
Transcription Factors

Keywords

  • EMT
  • Midline epithelial seam
  • Palate
  • Smad
  • TGFβ

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Dentistry(all)
  • Cell Biology

Cite this

Transforming growth factor β (TGFβ) signalling in palatal growth, apoptosis and epithelial mesenchymal transformation (EMT). / Nawshad, A.; Lagamba, D.; Hay, E. D.

In: Archives of Oral Biology, Vol. 49, No. 9, 01.09.2004, p. 675-689.

Research output: Contribution to journalReview article

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