Genetic interactions between activin type IIB receptor and Smad2 genes in asymmetrical patterning of the thoracic organs and the development of pancreas islets

Yutaka Goto, Masatoshi Nomura, Kimitaka Tanaka, Akiyo Kondo, Hidetaka Morinaga, Taijirou Okabe, Toshihiko Yanase, Hajime Nawata, Ryoichi Takayanagi, En Li

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Signaling through activin type IIB receptor (ActRIIB) has been shown to regulate the axial formation and the development of foregut-derived organs such as the pancreas in mice. Here, we provide genetic evidence that ActRIIB and Smad2 genes cooperatively regulated asymmetrical patterning of the thoracic organs and pancreas development in mice. The loss of one allele of Smad2 on ActRIIB-/- background resulted in the increased severity of ActRIIB-/- phenotypes, including right pulmonary isomerism and complex cardiac malformations, and resulted in 100% frequency of death soon after birth. Of interest, 14% of compound heterozygous ActRIIB +/-Smad2+/- mice exhibited the ActRIIB-/- phenotypes and died soon after birth. In the pancreas, hypoplastic islets were found not only in ActRIIB-/- but also in Smad2+/- mice. A more severe phenotype was also found in ActRIIB+/-Smad2+/- mice. As well, these mutant mice exhibited impaired glucose tolerance in a gene dosage-sensitive manner. This genetic evidence strongly suggested that ActRIIB and Smad2 function in the same signaling pathway to regulate axial patterning and pancreas islet formation by means of a threshold mechanism.

Original languageEnglish
Pages (from-to)2865-2874
Number of pages10
JournalDevelopmental Dynamics
Volume236
Issue number10
DOIs
Publication statusPublished - Oct 2007

All Science Journal Classification (ASJC) codes

  • Developmental Biology

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