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Dev Cell. 2008 Jun;14(6):877-89. doi: 10.1016/j.devcel.2008.03.021.

A regulatory network to segregate the identity of neuronal subtypes.

Author information

1
Department of Molecular Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. sklee@bcm.edu

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.

PMID:
18539116
PMCID:
PMC3071743
DOI:
10.1016/j.devcel.2008.03.021
[Indexed for MEDLINE]
Free PMC Article

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