Orthopedia Homeodomain Protein Is Essential for Diencephalic Dopaminergic Neuron Development

Soojin Ryu, Julia Mahler, Dario Acampora, Jochen Holzschuh, Simone Erhardt, Daniela Omodei, Antonio Simeone, Wolfgang Driever

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)873-880
Number of pages8
JournalCurrent Biology
Volume17
Issue number10
DOIs
Publication statusPublished - May 15 2007

Keywords

  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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    Ryu, S., Mahler, J., Acampora, D., Holzschuh, J., Erhardt, S., Omodei, D., Simeone, A., & Driever, W. (2007). Orthopedia Homeodomain Protein Is Essential for Diencephalic Dopaminergic Neuron Development. Current Biology, 17(10), 873-880. https://doi.org/10.1016/j.cub.2007.04.003