A Regulatory Network to Segregate the Identity of Neuronal Subtypes

Seunghee Lee, Bora Lee, Kaumudi Joshi, Samuel L. Pfaff, Jae W. Lee, Soo Kyung Lee

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Spinal motor neurons (MNs) and V2 interneurons (V2-INs) are specified by two related LIM-complexes, MN-hexamer and V2-tetramer, respectively. Here we show how multiple parallel and complementary feedback loops are integrated to assign these two cell fates accurately. While MN-hexamer response elements (REs) are specific to MN-hexamer, V2-tetramer-REs can bind both LIM-complexes. In embryonic MNs, however, two factors cooperatively suppress the aberrant activation of V2-tetramer-REs. First, LMO4 blocks V2-tetramer assembly. Second, MN-hexamer induces a repressor, Hb9, which binds V2-tetramer-REs and suppresses their activation. V2-INs use a similar approach; V2-tetramer induces a repressor, Chx10, which binds MN-hexamer-REs and blocks their activation. Thus, our study uncovers a regulatory network to segregate related cell fates, which involves reciprocal feedforward gene regulatory loops.

Original languageEnglish (US)
Pages (from-to)877-889
Number of pages13
JournalDevelopmental Cell
Volume14
Issue number6
DOIs
StatePublished - Jun 10 2008

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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