Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors.
Inductive signaling leads to the coactivation of regulatory pathways for specifying general neuronal traits in parallel with instructions for neuronal subtype specification. Nevertheless, the mechanisms that ensure that these pathways are synchronized have not been defined. To address this, we examined how bHLH proteins Ngn2 and NeuroM controlling neurogenesis functionally converge with LIM-homeodomain (LIM-HD) factors Isl1 and Lhx3 involved in motor neuron subtype specification. We found that Ngn2 and NeuroM transcriptionally synergize with Isl1 and Lhx3 to specify motor neurons in the embryonic spinal cord and in P19 stem cells. The mechanism underlying this cooperativity is based on interactions that directly couple the activity of the bHLH and LIM-HD proteins, mediated by the adaptor protein NLI. This functional link acts to synchronize neuronal subtype specification with neurogenesis.
Lee
Soo Kyung
SK
Gene Expression Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Pfaff
Samuel L
SL
D000818:Animals; D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D004742:Enhancer Elements, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D014157:Transcription Factors; C102084:Ldb1 protein, mouse; C094898:Lhx3 protein; C108527:NeuroM protein, chicken; C102938:Neurog2 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1