A Secreted Integrin-beta-like Molecule Itgbl-1 Modulates Integrin-ECM Interactions for the Cartilage Formation.

Abstract

Craniofacial development is among the most complicated processes in vertebrate development. In an effort to identify novel genes involved in facial development, we analyzed the transcriptome profiles of pharyngeal arches by performing RNAseq experiments. Several dozens of genes were strongly expressed in the first pharyngeal arch. Among them, a secreted integrin beta like molecule Itgbl-1 is specifically expressed in the cartilage tissues of the first pharyngeal arch. Morpholino-mediated knockdown of Itgbl-1 caused hypoplastic facial cartilages. Especially, the maxillary tissues were severely affected rather than mandibular, or hyoid cartilages. Furthermore overexpression of Itgbl1 accelerated cartilage formation resulting in significantly enlarged craniofacial cartilages. Further analysis revealed that Itgbl1 plays central roles in the integrin dependent signaling cascade for cartilage differentiation. Igbl1 seemed to reduce the integrin-ECM interactions and thereby inhibits stable focal adhesion formation in developing cartilage cells. In this study, we provide the first evidences for the molecular functions of Itgbl1 as a unique secreted modulator for the integrin-ECM interactions.