A history and interaction of outflow progenitor cells implicated in “takao syndrome”

Hiroyuki Yamagishi, Kazuki Kodo, Jun Maeda, Keiko Uchida, Takatoshi Tsuchihashi, Akimichi Shibata, Reina Ishizaki, Chihiro Yamagishi, Deepak Srivastava

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)


Progenitor cells, derived from the cardiac neural crest (CNC) and the second heart field (SHF), play key roles in development of the cardiac outflow tract (OFT), and their interaction is essential for establishment of the separate pulmonary and systemic circulation in vertebrates. 22q11.2 deletion syndrome (22q11DS) or Takao syndrome is the most common human chromosomal deletion syndrome that is highly associated with OFT defects. Historically, based on the observations in animal models, OFT defects implicated in the 22q11/Takao syndrome are believed to result primarily from abnormal development of CNC that populate into the conotruncal region of the heart. In the twenty-first century, elegant efforts to model 22q11/Takao syndrome in mice succeeded in the identification of T-box-containing transcription factor, Tbx1, as an etiology of OFT defects in this syndrome. Subsequent investigations of the Tbx1 expression pattern revealed that Tbx1 was surprisingly not detectable in CNC but was expressed in the SHF and provided a new concept of molecular and cellular basis for OFT defects associated with 22q11/Takao syndrome. More recently, it was reported that mutations in the gene encoding the transcription factor GATA6 caused CHD characteristic of OFT defects. Genes encoding the neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin A2 (PLXNA2) appear to be regulated directly by GATA6. Elucidation of molecular mechanism involving GATA6, SEMA3C, PLXNA2, and TBX1 in the interaction between the CNC and the SHF would provide new insights into the OFT development.

Original languageEnglish
Title of host publicationEtiology and Morphogenesis of Congenital Heart Disease
Subtitle of host publicationFrom Gene Function and Cellular Interaction to Morphology
PublisherSpringer Japan
Number of pages9
ISBN (Electronic)9784431546283
ISBN (Print)9784431546276
Publication statusPublished - 2016 Jan 1


  • 22q11.2 deletion syndrome
  • Congenital heart disease
  • GATA6
  • Neural crest
  • Second heart field

ASJC Scopus subject areas

  • General Medicine
  • General Biochemistry,Genetics and Molecular Biology


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