RGD Reference Report - A regulatory network to segregate the identity of neuronal subtypes. - Rat Genome Database

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A regulatory network to segregate the identity of neuronal subtypes.

Authors: Lee, Seunghee  Lee, Bora  Joshi, Kaumudi  Pfaff, Samuel L  Lee, Jae W  Lee, Soo-Kyung 
Citation: Lee S, etal., Dev Cell. 2008 Jun;14(6):877-89. doi: 10.1016/j.devcel.2008.03.021.
RGD ID: 155230693
Pubmed: PMID:18539116   (View Abstract at PubMed)
PMCID: PMC3071743   (View Article at PubMed Central)
DOI: DOI:10.1016/j.devcel.2008.03.021   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mnx1Ratnegative regulation of transcription by RNA polymerase II involved_inIDA PMID:18539116UniProt 
Isl1Ratpositive regulation of transcription by RNA polymerase II involved_inIGIUniProtKB:P50481PMID:18539116UniProt 

Cellular Component

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Isl1Rattranscription regulator complex part_ofIDA PMID:18539116UniProt 

Molecular Function


Objects Annotated

Genes (Rattus norvegicus)
Isl1  (ISL LIM homeobox 1)
Mnx1  (motor neuron and pancreas homeobox 1)

Additional Information