AUTHOR=Veistinen Lotta , Takatalo Maarit , Kesper Dörthe A., Vortkamp Andrea , Rice David P.

TITLE=Deletion of Gli3 in mice causes abnormal frontal bone morphology and premature synostosis of the interfrontal suture

JOURNAL=Frontiers in Physiology

VOLUME=3

YEAR=2012

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2012.00121

DOI=10.3389/fphys.2012.00121

ISSN=1664-042X

ABSTRACT=<p>Greig cephalopolysyndactyly syndrome (GCPS) is an autosomal dominant disorder with polydactyly and syndactyly of the limbs and a broad spectrum of craniofacial abnormalities. Craniosynostosis of the metopic suture (interfrontal suture in mice) is an important but rare feature associated with GCPS. GCPS is caused by mutations in the transcription factor <italic>GLI3</italic>, which regulates Hedgehog signaling. The <italic>Gli3</italic> loss-of-function (<italic>Gli3<sup>Xt-J/Xt-J</sup></italic>) mouse largely phenocopies the human syndrome with the mice exhibiting polydactyly and several craniofacial abnormalities. Here we show that <italic>Gli3<sup>Xt-J/Xt-J</sup></italic> mice exhibit ectopic ossification in the interfrontal suture and in the most severe cases the suture fuses already prior to birth. We show that abnormalities in frontal bones occur early in calvarial development, before the establishment of the interfrontal suture. It provides a model for the metopic suture pathology that can occur in GCPS.</p>