Biomedical subjects

Sylvia R Alappat

Publications and source records attributed to Sylvia R Alappat.

2 recordsLinked to original sources

PubMed2005

The cellular and molecular etiology of the cleft secondary palate in Fgf10 mutant mice.

Mammalian palatogenesis depends on interactions between the stomodium-derived epithelium and the cranial neural crest-derived ectomesenchyme. Fibroblast growth factor 10 (FGF10) is a mesenchymal signaling factor that guides the morphogenesis of multiple organs through tissue-tissue interactions. This is consistent with widespread agenesis and dysgenesis of organs observed in Fgf10-/- mice. In this study, we report the presence of a wide-open cleft secondary palate in Fgf10 homozygous null mutant mice. Fgf10 transcripts were detected in the palatal mesenchyme from E11.5 to E13.5 during normal palatogenesis and were enriched in the anterior and middle portions of the palatal shelves. In Fgf10-/- embryos, histological analyses revealed aberrant adhesion of the palatal shelves with the tongue in the anterior and fusion with the mandible in the middle and posterior beginning at E13.5, which could prevent normal elevation of the palatal shelves leading to a cleft palate. TUNEL and BrdU assays demonstrated significant levels of apoptosis in the medial edge epithelium (MEE) but unaltered cell proliferation in mutant palatal shelves. At the molecular level, we show that Fgf10 is epistatic to Jagged2 and Tgfbeta3 in the developing palate. Notably, the expression of Jagged2 is downregulated throughout the palate epithelium in Fgf10 mutants while Tgfbeta3 is misexpressed in the palatal epithelium at the oral side. Our results demonstrate that mesenchymally expressed Fgf10 is necessary for the survival of MEE cells and for the normal expression of Jagged2 and Tgfbeta3 in the palatal epithelium during mammalian palatogenesis.

Animals↗

PubMed2003

Mouse pigpen encodes a nuclear protein whose expression is developmentally regulated during craniofacial morphogenesis.

Pigpen, a nuclear protein with RNA-binding motifs and a putative transcriptional activation domain (TAD), is expressed at high levels in proliferating endothelial cells and expression is down-regulated when cells adopt a quiescent or differentiated phenotype. We cloned the mouse homolog of pigpen and investigated the regulation of its expression during embryogenesis. In situ hybridization demonstrated that a broad pattern of pigpen expression became restricted during tooth formation in the mandible. In the eye, pigpen showed a spatial restriction to the more proliferating and less differentiated regions of the lens and neural retina. Expression was also restricted in the developing vibrissae, lung, and kidney, all sites where epithelial-mesenchymal interactions are vital for morphogenesis. In vitro assays, that focused on the mandible and tooth development, indicated that epithelial signals, mediated by fibroblast growth factor-8, were required to maintain pigpen expression in the mandibular mesenchyme, whereas bone morphogenetic protein-4 negatively regulated expression in that tissue during early odontogenesis. At the protein level, immunocytochemistry demonstrated that Pigpen was expressed diffusely in the cytoplasm and more concentratedly in focal granules within the nuclei of mouse embryonic cells. Lastly, CAT reporter assays showed that the N-terminus of mouse pigpen encodes an active TAD. These data suggest that mouse Pigpen may activate transcription in vivo in response to specific growth factor signals and regulate proliferation and/or differentiation events during mouse organogenesis.

Amino Acid Sequence↗