| First Author | Joshi K | Year | 2009 |
| Journal | Neuron | Volume | 61 |
| Issue | 6 | Pages | 839-51 |
| PubMed ID | 19323994 | Mgi Jnum | J:147271 |
| Mgi Id | MGI:3840011 | Doi | 10.1016/j.neuron.2009.02.011 |
| Citation | Joshi K, et al. (2009) LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons. Neuron 61(6):839-51 |
| abstractText | Multiple excitatory and inhibitory interneurons form the motor circuit with motor neurons in the ventral spinal cord. Notch signaling initiates the diversification of immature V2-interneurons into excitatory V2a-interneurons and inhibitory V2b-interneurons. Here, we provide a transcriptional regulatory mechanism underlying their balanced production. LIM-only protein LMO4 controls this binary cell fate choice by regulating the activity of V2a- and V2b-specific LIM complexes inversely. In the spinal cord, LMO4 induces GABAergic V2b-interneurons in collaboration with SCL and inhibits Lhx3 from generating glutamatergic V2a-interneuons. In LMO4;SCL compound mutant embryos, V2a-interneurons increase markedly at the expense of V2b-interneurons. We further demonstrate that LMO4 nucleates the assembly of a novel LIM-complex containing SCL, Gata2, and NLI. This complex activates specific enhancers in V2b-genes consisting of binding sites for SCL and Gata2, thereby promoting V2b-interneuron fate. Thus, LMO4 plays essential roles in directing a balanced generation of inhibitory and excitatory neurons in the ventral spinal cord. |
