title: Orthopedia homeodomain protein is essential for diencephalic dopaminergic neuron development.
abstract: Neurons that produce dopamine as a neurotransmitter constitute a heterogeneous group involved in the control of various behaviors and physiology. In mammals, dopaminergic neurons are found in distinct clusters mainly located in the ventral midbrain and the caudal forebrain [1]. Although much is known about midbrain dopaminergic neurons, development of diencephalic dopaminergic neurons is poorly understood. Here we demonstrate that Orthopedia (Otp) homeodomain protein is essential for the development of specific subsets of diencephalic dopaminergic neurons. Zebrafish embryos lacking Otp activity are devoid of dopaminergic neurons in the hypothalamus and the posterior tuberculum. Similarly, Otp-/- mouse [2, 3] embryos lack diencephalic dopaminergic neurons of the A11 group, which constitutes the diencephalospinal dopaminergic system. In both systems, Otp is expressed in the affected dopaminergic neurons as well as in potential precursor populations, and it might contribute to dopaminergic cell specification and differentiation. In fish, overexpression of Otp can induce ectopic tyrosine hydroxylase and dopamine transporter expression, indicating that Otp can specify aspects of dopaminergic identity. Thus, Otp is one of the few known transcription factors that can determine aspects of the dopaminergic phenotype and the first known factor to control the development of the diencephalospinal dopaminergic system.
authors.affiliation: Department of Developmental Biology, Institute Biology 1, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
authors.forename: Soojin
authors.initials: S
authors.lastname: Ryu
authors.forename: Julia
authors.initials: J
authors.lastname: Mahler
authors.forename: Dario
authors.initials: D
authors.lastname: Acampora
authors.forename: Jochen
authors.initials: J
authors.lastname: Holzschuh
authors.forename: Simone
authors.initials: S
authors.lastname: Erhardt
authors.forename: Daniela
authors.initials: D
authors.lastname: Omodei
authors.forename: Antonio
authors.initials: A
authors.lastname: Simeone
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Driever
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004027:Diencephalon / Q000166:cytology / Q000196:embryology*; D004298:Dopamine / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C088624:Otp protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C515950:orthopedia protein, zebrafish; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine