Gata3 participates in a complex transcriptional feedback network to regulate sympathoadrenal differentiation

Takashi Moriguchi, Nakano Takako, Michito Hamada, Atsuko Maeda, Yuki Fujioka, Takashi Kuroha, Reuben E. Huber, Susan L. Hasegawa, Arvind Rao, Masayuki Yamamoto, Satoru Takahashi, Kim Chew Lim, James Douglas Engel

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

Gata3 mutant mice expire of noradrenergic deficiency by embryonic day (E) 11 and can be rescued pharmacologically or, as shown here, by restoring Gata3 function specifically in sympathoadrenal (SA) lineages using the human DBH promoter to direct Gata3 transgenic expression. In Gata3-null embryos, there was significant impairment of SA differentiation and increased apoptosis in adrenal chromaffin cells and sympathetic neurons. Additionally, mRNA analyses of purified chromaffin cells from Gata3 mutants show that levels of Mash 1, Hand2 and Phox2b (postulated upstream regulators of Gata3) as well as terminally differentiated SA lineage products (tyrosine hydroxylase, Th, and dopamine β-hydroxylase, Dbh) are markedly altered. However, SA lineage-specific restoration of Gata3 function in the Gata3 mutant background rescues the expression phenotypes of the downstream, as well as the putative upstream genes. These data not only underscore the hypothesis that Gata3 is essential for the differentiation and survival of SA cells, but also suggest that their differentiation is controlled by mutually reinforcing feedback transcriptional interactions between Gata3, Mash1, Hand2 and Phox2b in the SA lineage.

Original languageEnglish
Pages (from-to)3871-3881
Number of pages11
JournalDevelopment
Volume133
Issue number19
DOIs
Publication statusPublished - 2006 Oct
Externally publishedYes

Keywords

  • Chromaffin cells
  • Dopamine β-hydroxylase
  • Gata3
  • Sympathetic neurons
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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