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Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia.
Development. 2007 Dec; 134(24):4417-26.D

Abstract

In the developing hypothalamus, a variety of neurons are generated adjacent to each other in a highly coordinated, but poorly understood process. A critical question that remains unanswered is how coordinated development of multiple neuronal types is achieved in this relatively narrow anatomical region. We focus on dopaminergic (DA) and oxytocinergic (OT) neurons as a paradigm for development of two prominent hypothalamic cell types. We report that the development of DA and OT-like neurons in the zebrafish is orchestrated by two novel pathways that regulate the expression of the homeodomain-containing protein Orthopedia (Otp), a key determinant of hypothalamic neural differentiation. Genetic analysis showed that the G-protein-coupled receptor PAC1 and the zinc finger-containing transcription factor Fezl act upstream to Otp. In vivo and in vitro experiments demonstrated that Fezl and PAC1 regulate Otp at the transcriptional and the post-transcriptional levels, respectively. Our data reveal a new genetic network controlling the specification of hypothalamic neurons in vertebrates, and places Otp as a critical determinant underlying Fezl- and PAC1-mediated differentiation.

Authors+Show Affiliations

Department of Molecular Cell Biology, Weizmann Institute of Science, PO Box 26, Rehovot 76100, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18003738

Citation

Blechman, Janna, et al. "Specification of Hypothalamic Neurons By Dual Regulation of the Homeodomain Protein Orthopedia." Development (Cambridge, England), vol. 134, no. 24, 2007, pp. 4417-26.
Blechman J, Borodovsky N, Eisenberg M, et al. Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia. Development. 2007;134(24):4417-26.
Blechman, J., Borodovsky, N., Eisenberg, M., Nabel-Rosen, H., Grimm, J., & Levkowitz, G. (2007). Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia. Development (Cambridge, England), 134(24), 4417-26.
Blechman J, et al. Specification of Hypothalamic Neurons By Dual Regulation of the Homeodomain Protein Orthopedia. Development. 2007;134(24):4417-26. PubMed PMID: 18003738.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia. AU - Blechman,Janna, AU - Borodovsky,Nataliya, AU - Eisenberg,Mark, AU - Nabel-Rosen,Helit, AU - Grimm,Jan, AU - Levkowitz,Gil, Y1 - 2007/11/14/ PY - 2007/11/16/pubmed PY - 2008/2/21/medline PY - 2007/11/16/entrez SP - 4417 EP - 26 JF - Development (Cambridge, England) JO - Development VL - 134 IS - 24 N2 - In the developing hypothalamus, a variety of neurons are generated adjacent to each other in a highly coordinated, but poorly understood process. A critical question that remains unanswered is how coordinated development of multiple neuronal types is achieved in this relatively narrow anatomical region. We focus on dopaminergic (DA) and oxytocinergic (OT) neurons as a paradigm for development of two prominent hypothalamic cell types. We report that the development of DA and OT-like neurons in the zebrafish is orchestrated by two novel pathways that regulate the expression of the homeodomain-containing protein Orthopedia (Otp), a key determinant of hypothalamic neural differentiation. Genetic analysis showed that the G-protein-coupled receptor PAC1 and the zinc finger-containing transcription factor Fezl act upstream to Otp. In vivo and in vitro experiments demonstrated that Fezl and PAC1 regulate Otp at the transcriptional and the post-transcriptional levels, respectively. Our data reveal a new genetic network controlling the specification of hypothalamic neurons in vertebrates, and places Otp as a critical determinant underlying Fezl- and PAC1-mediated differentiation. SN - 0950-1991 UR - https://www.unboundmedicine.com/medline/citation/18003738/Specification_of_hypothalamic_neurons_by_dual_regulation_of_the_homeodomain_protein_Orthopedia_ L2 - http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=18003738 DB - PRIME DP - Unbound Medicine ER -