Isl1Cre reveals a common Bmp pathway in heart and limb development

Research output: Contribution to journalArticlepeer-review

Authors

  • Lei Yang
  • Chen Leng Cai
  • Lizhu Lin
  • Yibing Qyang
  • Christine Chung
  • Christine L. Mummery
  • Glenn I. Fishman
  • Anna Cogen
  • Sylvia Evans

Colleges, School and Institutes

External organisations

  • University of California, San Diego
  • Harvard Medical School
  • Wellman Center for Photomedicine
  • Hubrecht Institute
  • Interuniversity Cardiology Institute of the Netherlands (ICIN)
  • NYU Langone Medical Center
  • New York University

Abstract

A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an IsI1Cre mouse line to demonstrate that IsI1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, IsI1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in IsI1-expressing progenitors, we ablated the Type l Bmp receptor, Bmpr1a utilizing Isl1Crel+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo.

Details

Original languageEnglish
Pages (from-to)1575-1585
Number of pages11
JournalDevelopment
Volume133
Issue number8
Publication statusPublished - 1 Apr 2006

Keywords

  • Bmp, Heart, Hindlimb, Isl1, Tbx2, Tbx3