Embryonic expression of EphA receptor genes in mice supports their candidacy for involvement in cleft lip and palate. Issue 11 (14th August 2014)

• Record Type: Journal Article
• Authors: Agrawal, Puja; Wang, Michael; Kim, Seungil; Lewis, Ace E.; Bush, Jeffrey O.
• Is Part Of: Developmental dynamics. Volume 243:Issue 11(2014:Nov.)
• Page Start: 1470
• Page End: 1476
• Publication Date: 2014-08-14
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24170
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <underline>Background:</underline> Eph receptors, comprising the A‐ and B‐subfamilies, are the largest family of receptor tyrosine kinases in the mammalian genome, and their function is critical for morphogenesis in a variety of contexts. Whereas signaling through B‐type Ephs has been demonstrated to play a role in cleft lip and palate (CL/P), the involvement of A‐type Ephs has not been examined in this context notwithstanding a recent genome‐wide association study that identified the <italic>EPHA3</italic> locus as a candidate for non‐syndromic CL/P. <underline>Results:</underline> Here, we present a systematic analysis of the gene expression patterns for the nine EphA receptors at progressive stages of mouse development and find that <italic>EphA3, EphA4</italic>, and <italic>EphA7</italic> exhibit restricted overlapping patterns of expression during palate development. We find that homozygous mutation of <italic>EphA3</italic> or compound homozygous mutation of <italic>EphA3</italic> and <italic>EphA4</italic> in mice does not result in defective midfacial development, supporting the possibility of redundant function with <italic>EphA7</italic>. We also document previously undescribed expression patterns in other tissues of the craniofacial complex including the lacrimal duct and salivary glands. <underline>Conclusions:</underline> Together, these results are consistent with the hypothesis that mutations in <italic>EPHA</italic> family genes may cause CL/P and also suggest that functional redundancy between family members may be at play. <italic>Developmental Dynamics 243:1470–1476, 2014</italic>. © 2014 Wiley Periodicals, Inc.</p> </abstract>