title: Phox2b influences the development of a caudal dopaminergic subset.
abstract: The developing mesodiencephalic dopaminergic (mdDA) neuronal field can be subdivided into several molecularly distinct domains that arise due to spatiotemporally distinct origins of the neurons and distinct transcriptional pathways controlling these neuronal subsets. Two large anatomically and functionally different subdomains are formed that eventually give rise to the SNc and VTA, but more subsets exist which require detailed characterization in order to better understand the development of the functionally different mdDA subsets, and subset-specific vulnerability. In this study, we aimed to characterize the role of transcription factor Phox2b in the development of mdDA neurons. We provide evidence that Phox2b is co-expressed with TH in a dorsal-caudal subset of neurons in the mdDA neuronal field during embryonic development. Moreover, Phox2b transcripts were identified in FAC-sorted Pitx3 positive neurons. Subsequent analysis of Phox2b mutant embryos revealed that in the absence of Phox2b, a decrease of TH expression occurred specifically in the midbrain neuronal subset that normally co-expresses Phox2b with TH. Our data suggest that Phox2b is, next to the known role in the development of the oculomotor complex, involved in the development of a specific caudal mdDA neuronal subset.
authors.affiliation: Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Elisa J
authors.initials: EJ
authors.lastname: Hoekstra
authors.forename: Lars
authors.initials: L
authors.lastname: von Oerthel
authors.forename: Annemarie J A
authors.initials: AJ
authors.lastname: van der Linden
authors.forename: Marten P
authors.initials: MP
authors.lastname: Smidt
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D013126:Spinal Nerve Roots / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism / Q000502:physiology; D017557:Ventral Tegmental Area / Q000378:metabolism / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D014157:Transcription Factors; C433629:homeobox protein PITX3