RRC ID 11825
Author García-Frigola C, Herrera E.
Title Zic2 regulates the expression of Sert to modulate eye-specific refinement at the visual targets.
Journal EMBO J.
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.
Volume 29(18)
Pages 3170-83
Published 2010-9-15
DOI 10.1038/emboj.2010.172
PII emboj2010172
PMID 20676059
PMC PMC2944059
MeSH Animals Axons / physiology* Biomarkers / metabolism Blotting, Western Chromatin Immunoprecipitation Female Gene Expression Profiling Gene Expression Regulation, Developmental* Immunoenzyme Techniques Mice Mice, Knockout Oligonucleotide Array Sequence Analysis RNA, Messenger / genetics Retinal Ganglion Cells / physiology* Reverse Transcriptase Polymerase Chain Reaction Serotonin Plasma Membrane Transport Proteins / genetics* Serotonin Plasma Membrane Transport Proteins / metabolism Transcription Factors / physiology*
IF 11.227
Times Cited 22
Mice C57BL/6N-Kd(Zic2)