Activin Subunit and Receptor Expression in Normal and Cleft Human Fetal Palate Tissues

Abstract

Craniofacial malformations, such as cleft palate, present serious complications in the newborn and are often of unknown etiology. Activin BA subunit deletion leads to cleft palate in mice, but the expression of this protein in the human palate has not been explored. Our goal was to determine the spatial and temporal expression of inhibin/activin subunits; the binding protein, follistatin; and activin receptors in the human fetal palate. Residual human fetal palate tissues, with or without cleft, were collected during routine autopsy at Women and Infants Hospital. Inhibin/activin alpha and beta subunits, follistatin, and activin receptor protein and mRNA expression were studied by immunocytochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) experiments, respectively. Dimeric activin A levels were compared in cleft and normal palate tissue homogenates by immunoassay. Activin BA, follistatin, and activin receptor type IIA proteins were observed in normal and cleft palate tissues throughout pregnancy (gestational weeks 11 to 40). Proteins were predominantly found in developing bone cells, with no significant group differences. Inhibin/activin BA subunit, follistatin, and activin receptor mRNAs were also detected in normal and cleft fetal palate tissues, but inhibin alpha and BB subunit were absent. Inhibin/activin BA subunit expression was consistent with the presence of dimeric activin A, but levels did not differ significantly between cleft and control tissues. Inhibin/activin BA subunit, follistatin, and activin receptor proteins and mRNAs are present in the human fetal palate. These data suggest that activin signalling has the potential to be associated with human palate development.