AUTHOR=Kulkarni Anshul K. , Louie Ke’ale W. , Yatabe Marilia , Ruellas Antonio Carlos de Oliveira , Mochida Yoshiyuki , Cevidanes Lucia H. S. , Mishina Yuji , Zhang Honghao 

TITLE=A Ciliary Protein EVC2/LIMBIN Plays a Critical Role in the Skull Base for Mid-Facial Development

JOURNAL=Frontiers in Physiology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.01484

DOI=10.3389/fphys.2018.01484

ISSN=1664-042X

ABSTRACT=Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplastic disorder. Affected patients present a wide spectrum of symptoms including short stature, postaxial polydactyly, and dental abnormalities. We previously disrupted Evc2, one of the causative genes for EvC syndrome, in a neural crest-specific manner in mice using a neural crest specific P0-Cre (Evc2 P0 mutants) and reported that despite the fact that P0-Cre well targets to the mid-facial region, many mid-facial defects identified in the Evc2 global mutants are not present in the Evc2 P0 mutants at postnatal day 8 (P8). In the current study, we used both P0-Cre and Wnt1-Cre, respectively, to specifically delete Evc2 in the neural crest-derived tissues and compared the resulted mid-facial defects at P8 and P28. While both Cre lines indistinguishably targeted the mid-facial region, they differentially targeted the anterior portion of the skull base. By comprehensively analyzing the shapes of conditional mutant skulls, we detected differentially affected mid-facial defects in Evc2 P0 mutants and Evc2 Wnt1 mutants. Micro-CT analysis of the skull base further revealed that the Evc2 mutation leads to a differentially affected skull base, caused by premature closure of the intersphenoid synchondrosis (presphenoidal synchondrosis), which limited the elongation of the anterior skull base during the postnatal development of the skull. Given the importance of the skull base in mid-facial bone development, our results suggest that loss of function of Evc2 within the skull base secondarily leads to many aspects of the mid-facial defects developed by the EvC syndrome.