Ding YQ, Marklund U, Yuan W, Yin J, Wegman L, Ericson Johan, Deneris E, Johnson RL, and Chen ZF. (2003) Lmx1b is essential for the development of serotonergic neurons. Nat. Neurosci. 6(9): 933-938. PMID: 12897786
The specification and differentiation of serotonergic (5-HT) neurons require both extrinsic signaling molecules and intrinsic transcription factors to work in concert or in cascade. Here we identify the genetic cascades that control the specification and differentiation of 5-HT neurons in mice. A major determinant in the cascades is an LIM homeodomain-containing gene, Lmx1b, which is required for the development of all 5-HT neurons in the central nervous system. Our results suggest that, during development of 5-HT neurons, Lmx1b is a critical intermediate factor that couples Nkx2-2-mediated early specification with Pet1-mediated terminal differentiation. Moreover, our data indicate that genetic cascades controlling the caudal and rostral 5-HT neurons are distinct, despite their shared components.