Mutations in IRX5 impair craniofacial development and germ cell migration via SDF1

Carine Bonnard, Anna C. Strobl, Mohammad Shboul, Hane Lee, Barry Merriman, Stanley F. Nelson, Osama H. Ababneh, Elif Uz, Tülay Güran, Hülya Kayserili, Hanan Hamamy, Bruno Reversade

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Using homozygosity mapping and locus resequencing, we found that alterations in the homeodomain of the IRX5 transcription factor cause a recessive congenital disorder affecting face, brain, blood, heart, bone and gonad development. We found through in vivo modeling in Xenopus laevis embryos that Irx5 modulates the migration of progenitor cell populations in branchial arches and gonads by repressing Sdf1. We further found that transcriptional control by Irx5 is modulated by direct protein-protein interaction with two GATA zinc-finger proteins, GATA3 and TRPS1; disruptions of these proteins also cause craniofacial dysmorphisms. Our findings suggest that IRX proteins integrate combinatorial transcriptional inputs to regulate key signaling molecules involved in the ontogeny of multiple organs during embryogenesis and homeostasis. © 2012 Nature America, Inc. All rights reserved.
Original languageEnglish (US)
Pages (from-to)709-713
Number of pages5
JournalNature Genetics
Volume44
Issue number6
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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