TGF-beta3 is required for the adhesion and intercalation of medial edge epithelial cells during palate fusion.
Transforming growth factor-beta3 (TGF-beta3) plays a critical role during palate development, since mutations of the TGF-beta3 gene give rise to cleft palate in both humans and mice. Striking alterations have been reported in the behaviour and differentiation of medial edge epithelial (MEE) cells in TGF-beta3 knockout mouse palates. In the present paper, we provide evidence of alterations in MEE intercellular adhesion in TGF-beta3 -/- mouse palates using immunohistochemistry with monoclonal antibodies to a panel of cell adhesion and cytoskeletal molecules including E-cadherin, alpha and beta catenin, beta actin, vinculin and beta2 integrin. In vitro labeling of opposing MEE with two different lipophilic markers and subsequent analysis by confocal microscopy revealed that wild type MEE cells intercalate as soon as the midline epithelial seam forms. This finding indicates that the palate may elongate in a dorso-ventral direction by means of convergent extension, as occurs in other embryonic developmental processes. In contrast, this intercalation does not occur in the TGF-beta3 -/- MEE but it can be rescued by the exogenous addition of TGF-beta3. Thus, the substantial alteration of MEE intercellular adhesion observed in TGF-beta3 -/- palates may account for the defect in palatal shelf adhesion and the formation of cleft palate.
Tudela
Consuelo
C
Departamento de Ciencias Morfológicas I, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Formoso
Miguel-Angel
MA
Martínez
Tamara
T
Pérez
Raquel
R
Aparicio
Marta
M
Maestro
Carmen
C
Del Río
Aurora
A
Martínez
Elena
E
Ferguson
Mark
M
Martínez-Alvarez
Concepción
C
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D005314:Embryonic and Fetal Development; D004847:Epithelial Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010159:Palate / Q000196:embryology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053782:Transforming Growth Factor beta3
C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3