Disruption of gradient expression of Zic3 resulted in abnormal intra-retinal axon projection.
The targeting of retinal ganglion axons toward the optic disc is the first step in axon pathfinding in the visual system. The molecular mechanisms involved in guiding the retinal axons to project towards the optic disc are not well understood. We report that a gene encoding a zinc-finger transcription factor, Zic3, is expressed in a periphery-high and center-low gradient in the retina at the stages of active axon extension inside the retina. The gradient expression of Zic3 recedes towards the periphery over the course of development, correlating with the progression of retinal cell differentiation and axonogenesis. Disruption of gradient expression of Zic3 by retroviral overexpression resulted in mis-targeting of retinal axons and some axons misrouted to the sub-retinal space at the photoreceptor side of the retina. Misexpression of Zic3 did not affect neurogenesis or differentiation inside the retina, or grossly alter retinal lamination. By stripe assay, we show that misexpression of Zic3 may induce the expression of an inhibitory factor to the retinal axons. Zic3 appears to play a role in intra-retinal axon targeting, possibly through regulation of the expression of specific downstream genes involved in axon guidance.
Department of Medicine and Cell Biology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
Jinhua
J
Zhang
Zhe
Z
Jin
Zheng-Zheng
ZZ
Bao
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo / Q000033:anatomy & histology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D009024:Morphogenesis; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D010641:Phenotype; D012160:Retina / Q000033:anatomy & histology* / Q000196:embryology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C491595:ZIC3 protein, human; D000075388:Netrin-1