Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis

d'Amaro, Rocca; Scheidegger, Rolf; Blumer, Susanne; Pazera, Pawel; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias (2012). Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis. Frontiers in physiology, 3, p. 377. Lausanne: Frontiers Research Foundation 10.3389/fphys.2012.00377

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Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf-β/Bmp activity.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > School of Dental Medicine > Department of Orthodontics

UniBE Contributor:

Blumer, Susanne; Pazera, Pawel; Katsaros, Christos and Chiquet, Matthias

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-042X

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Eveline Carmen Schuler

Date Deposited:

04 Oct 2013 14:30

Last Modified:

25 Jan 2017 12:16

Publisher DOI:

10.3389/fphys.2012.00377

PubMed ID:

23055981

BORIS DOI:

10.7892/boris.11285

URI:

https://boris.unibe.ch/id/eprint/11285 (FactScience: 217363)

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