title: LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons.
abstract: 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.
authors.affiliation: Department of Molecular Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Kaumudi
authors.initials: K
authors.lastname: Joshi
authors.forename: Seunghee
authors.initials: S
authors.lastname: Lee
authors.forename: Bora
authors.initials: B
authors.lastname: Lee
authors.forename: Jae W
authors.initials: JW
authors.lastname: Lee
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Lee