Lmx1b is essential for the development of serotonergic neurons.
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.
Ding
Yu-Qiang
YQ
Department of Anesthesiology, School of Medicine Pain Center, Washington University, St. Louis, Missouri 63110, USA.
Marklund
Ulrika
U
Yuan
Wenlin
W
Yin
Jun
J
Wegman
Lauren
L
Ericson
Johan
J
Deneris
Evan
E
Johnson
Randy L
RL
Chen
Zhou-Feng
ZF
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; C000715627:Nkx2-2 protein, mouse; D014157:Transcription Factors; D012701:Serotonin