Numerous transcription factors regulate the generation and migration of neurons during the development of the central nervous system but the co-factors that support their activity remain unclear. Here (p. ), Soo-Kyung Lee and co-workers identify the LIM-only protein LMO4 as a co-activator of the proneural transcription factor neurogenin 2 (NGN2) in the developing mouse cortex. The researchers show that LMO4 and its binding partner nuclear LIM interactor (NLI) form a multi-protein transcription complex with NGN2. This complex, they report, is recruited to the E-box-containing enhancers of NGN2 target genes, which regulate various aspects of cortical development, and activates NGN2-mediated transcription. Consistent with this finding, the researchers demonstrate that neuronal differentiation is impaired in the cortex of Lmo4-null embryos, whereas expression of LMO4 facilitates NGN2-mediated migration and differentiation of neurons in the embryonic cortex. These results suggest that the LMO4:NLI module promotes the acquisition of cortical neuronal identities by forming a complex with NGN2 and subsequently activating NGN2-dependent gene expression.
