TY - JOUR
T1 - Transforming growth factor β (TGFβ) signalling in palatal growth, apoptosis and epithelial mesenchymal transformation (EMT)
AU - Nawshad, A.
AU - Lagamba, D.
AU - Hay, E. D.
N1 - Funding Information:
The original research described in this review was supported by NIH R01-DE11142 from the US public health service. We thank Caroline Chui for her help preparing the manuscript and figures.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - EMT
KW - Midline epithelial seam
KW - Palate
KW - Smad
KW - TGFβ
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U2 - 10.1016/j.archoralbio.2004.05.007
DO - 10.1016/j.archoralbio.2004.05.007
M3 - Review article
C2 - 15275855
AN - SCOPUS:3342934231
SN - 0003-9969
VL - 49
SP - 675
EP - 689
JO - Archives of Oral Biology
JF - Archives of Oral Biology
IS - 9
ER -