NDLI: A trans-Regulatory Code for the Forebrain Expression of Six3.2 in the Medaka Fish.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Conte, Ivan Wittbrodt, Jochen Manfredi, Anna Bovolenta, Paola Beccari, Leonardo Tabanera, Noemi Souren, Marcel Wittbrodt, Beate Marco-ferreres, Raquel
Description	Author Affiliation: Beccari L ( From the Centro de Biología Molecular 'Severo Ochoa,' Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, c/ Nicolas Cabrera 1, Madrid 28049, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), c/ Nicolas Cabrera 1, Madrid 28049, Spain, In); Marco-Ferreres R ( From the Centro de Biología Molecular 'Severo Ochoa,' Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, c/ Nicolas Cabrera 1, Madrid 28049, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), c/ Nicolas Cabrera 1, Madrid 28049, Spain, In); Tabanera N ( From the Centro de Biología Molecular 'Severo Ochoa,' Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, c/ Nicolas Cabrera 1, Madrid 28049, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), c/ Nicolas Cabrera 1, Madrid 28049, Spain, In); Manfredi A ( Instituto Cajal, Consejo Superior de Investigaciones Científicas, Avda. Dr. Arce 37, Madrid, 28002, Spain.); Souren M ( the Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.); Wittbrodt B ( the Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.); Conte I ( Instituto Cajal, Consejo Superior de Investigaciones Científicas, Avda. Dr. Arce 37, Madrid, 28002, Spain, the Telethon Institute of Genetics and Medicine, Via Campi Flegrei 34, Pozzuoli, Naples, 80078, Italy, and.); Wittbrodt J ( the Centre for Organismal Studies, University of Heidelberg, Im Neuenheimer Feld 230, 69120 Heidelberg, Germany.); Bovolenta P ( From the Centro de Biología Molecular 'Severo Ochoa,' Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, c/ Nicolas Cabrera 1, Madrid 28049, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), c/ Nicolas Cabrera 1, Madrid 28049, Spain, In)
Abstract	A well integrated and hierarchically organized gene regulatory network is responsible for the progressive specification of the forebrain. The transcription factor Six3 is one of the central components of this network. As such, Six3 regulates several components of the network, but its upstream regulators are still poorly characterized. Here we have systematically identified such regulators, taking advantage of the detailed functional characterization of the regulatory region of the medaka fish Six3.2 ortholog and of a time/cost-effective trans-regulatory screening, which complemented and overcame the limitations of in silico prediction approaches. The candidates resulting from this search were validated with dose-response luciferase assays and expression pattern criteria. Reconfirmed candidates with a matching expression pattern were also tested with chromatin immunoprecipitation and functional studies. Our results confirm the previously proposed direct regulation of Pax6 and further demonstrate that Msx2 and Pbx1 are bona fide direct regulators of early Six3.2 distribution in distinct domains of the medaka fish forebrain. They also point to other transcription factors, including Tcf3, as additional regulators of different spatial-temporal domains of Six3.2 expression. The activity of these regulators is discussed in the context of the gene regulatory network proposed for the specification of the forebrain.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	45
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-11-06
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Eye Proteins Genetics Fish Proteins Homeodomain Proteins Nerve Tissue Proteins Oryzias Embryology Prosencephalon Metabolism Animals Animals, Genetically Modified Body Patterning Gene Expression Regulation, Developmental Gene Regulatory Networks RNA, Messenger Transcription Factors Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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