LIM Homeobox Transcription Factor 1 Alpha (LMX1a)

Insulin is produced exclusively by the beta cells in the islets of Langerhans in the pancreas. The level and beta-cell specificity of insulin gene expression are regulated by a set of nuclear genes that bind to specific sequences within the promoter of the insulin gene INS and interact with RNA polymerase to activate or repress transcription. LMX1 is a LIM homeobox transcription factor that binds an A/T-rich sequence in the insulin promoter and stimulates transcription of insulin. Lmx1a was necessary and sufficient to trigger dopamine cell differentiation, and early activity of Lmx1a induced expression of Msx1, which complemented Lmx1a by inducing expression of Ngn2 (NEUROG2) and neuronal differentiation. Expression of Lmx1a in embryonic stem cells resulted in robust generation of dopamine neurons with midbrain identity.