title: Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons.
abstract: Serotonin (5-HT) neurons synthesize a variety of peptides. How these peptides are controlled during development remains unclear. It has been reported that the co-localization of peptides and 5-HT varies by species. In contrast to the situations in the rostral 5-HT neurons of human and rat brains, several peptides do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain. In this study, we found that the peptide substance P and peptide genes, including those encoding peptides thyrotropin-releasing hormone, enkephalin, and calcitonin gene-related peptide, were expressed in the caudal 5-HT neurons of mouse brain; these findings are in line with observations in rat and monkey 5-HT neurons. We also revealed that these peptides/peptide genes partially overlapped with the transcription factor Lmx1b that specifies the 5-HT cell fate. Furthermore, we found that the peptide cholecystokinin was expressed in developing dopaminergic neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell fate. By examining the phenotype of Lmx1b deletion mice, we found that Lmx1b was required for the expression of above peptides expressed in 5-HT or dopaminergic neurons. Together, our results indicate that Lmx1b, a key transcription factor for the specification of 5-HT and dopaminergic transmitter phenotypes during embryogenesis, determines some peptide phenotypes in these neurons as well.
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yan
authors.forename: Tianwen
authors.initials: T
authors.lastname: Huang
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Xie
authors.forename: Guannan
authors.initials: G
authors.lastname: Xia
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhao
authors.forename: Leping
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002116:Calcitonin / Q000096:biosynthesis; D002766:Cholecystokinin / Q000096:biosynthesis; D059290:Dopaminergic Neurons / Q000378:metabolism*; D004745:Enkephalins / Q000096:biosynthesis; D060850:LIM-Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D010487:Periaqueductal Gray / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D011498:Protein Precursors / Q000096:biosynthesis; D011903:Raphe Nuclei / Q000196:embryology / Q000378:metabolism; D059326:Serotonergic Neurons / Q000378:metabolism*; D013373:Substance P / Q000096:biosynthesis; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004745:Enkephalins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D011498:Protein Precursors; D014157:Transcription Factors; D013373:Substance P; D013973:Thyrotropin-Releasing Hormone; D002116:Calcitonin; D002766:Cholecystokinin; C033660:preproenkephalin