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    Dev Cell. 2008 Jun;14(6):877-89.

    A regulatory network to segregate the identity of neuronal subtypes.

    Lee S, Lee B, Joshi K, Pfaff SL, Lee JW, Lee SK.

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

    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 [PubMed - indexed for MEDLINE]

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