Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets

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Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets

This neurodevelopmental paper reports on the transcription factor Zic2 as critical regulator of visual target refinement. Establishing that Zic2 acts through the serotonin transporter SERT provides insight into a critical element of visual circuitry.

Abstract

The development of the nervous system is a time-ordered and multi-stepped process that requires neural specification, axonal navigation and arbor refinement at the target tissues. Previous studies have demonstrated that the transcription factor Zic2 is necessary and sufficient for the specification of retinal ganglion cells (RGCs) that project ipsilaterally at the optic chiasm midline. Here, we report that, in addition, Zic2 controls the refinement of eye-specific inputs in the visual targets by regulating directly the expression of the serotonin transporter (Sert), which is involved in the modulation of activity-dependent mechanisms during the wiring of sensory circuits. In agreement with these findings, RGCs that express Zic2 ectopically show defects in axonal refinement at the visual targets and respond to pharmacological blockage of Sert, whereas Zic2-negative contralateral RGCs do not. These results link, at the molecular level, early events in neural differentiation with late activity-dependent processes and propose a mechanism for the establishment of eye-specific domains at the visual targets.

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Most cited references 59

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Author and article information

Journal

Journal ID (nlm-ta): EMBO J

Title: The EMBO Journal

Publisher: Nature Publishing Group

ISSN (Print): 0261-4189

ISSN (Electronic): 1460-2075

Publication date (Print): 15 September 2010

Publication date (Electronic): 30 July 2010

Publication date PMC-release: 30 July 2010

Volume: 29

Issue: 18

Pages: 3170-3183

Affiliations

[1 ]simpleInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas & Universidad Miguel Hernandez , Alicante, Spain

Author notes

[a ]Department of Developmental Neurobiology, Instituto de Neurociencias de Alicante (CSIC-UMH), Avd Ramón y Cajal s/n, Alicante 03550, Spain. Tel.: +34 965 919231; Fax: +34 965 919200; E-mail: e.herrera@ 123456umh.es

Article

Publisher Item ID: emboj2010172

DOI: 10.1038/emboj.2010.172

PMC ID: 2944059

PubMed ID: 20676059

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.

Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets

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