PUBLICATION

Orthopedia Homeodomain Protein Is Essential for Diencephalic Dopaminergic Neuron Development

Authors
Ryu, S., Mahler, J., Acampora, D., Holzschuh, J., Erhardt, S., Omodei, D., Simeone, A., and Driever, W.
ID
ZDB-PUB-070513-14
Date
2007
Source
Current biology : CB   17(10): 873-880 (Journal)
Registered Authors
Driever, Wolfgang, Erhardt, Simone, Holzschuh, Jochen, Mahler, Julia, Ryu, Soojin
Keywords
none
MeSH Terms
  • Animals
  • Cell Differentiation
  • Diencephalon/cytology
  • Diencephalon/embryology*
  • Dopamine/metabolism
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Homeodomain Proteins/genetics
  • Homeodomain Proteins/metabolism
  • Homeodomain Proteins/physiology*
  • Mice
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/metabolism
  • Nerve Tissue Proteins/physiology
  • Neurons/cytology
  • Neurons/metabolism
  • Neurons/physiology*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Transcription Factors/physiology*
  • Tyrosine 3-Monooxygenase/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Zebrafish Proteins/physiology*
PubMed
17481897 Full text @ Curr. Biol.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping