title: A mouse model of aniridia reveals the in vivo downstream targets of Pax6 driving iris and ciliary body development in the eye.
abstract: The Pax6 transcription factor is essential for development of the brain, eye, olfactory and endocrine systems. Haploinsufficiency of PAX6 in humans and mice causes the congenital condition aniridia, with defects in each of these organs and systems. Identification of the PAX6 transcription networks driving normal development is therefore critical in understanding the pathophysiology observed with loss-of-function defects. Here we have focused on identification of the downstream targets for Pax6 in the developing iris and ciliary body, where we used laser capture microdissection in mouse eyes from E12.5-E16.5, followed by chromatin immunoprecipitation, promoter-reporter assays and immunohistochemistry. We identified 6 differentially expressed genes between wildtype and Pax6 heterozygous mouse tissues and demonstrated that Bmp4, Tgfβ2, and Foxc1 were direct downstream targets of Pax6 in developing iris/ciliary body. These results improve our understanding of how mutations in Bmp4, Tgfβ2, and Foxc1 result in phenocopies of the aniridic eye disease and provide possible targets for therapeutic intervention.
authors: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: Xia
authors: X
authors: Wang
authors: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
authors: Xianghong
authors: X
authors: Shan
authors: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address: cge30@mail.ubc.ca.
authors: Cheryl Y
authors: CY
authors: Gregory-Evans
mesh_terms: D000818:Animals; D015783:Aniridia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002924:Ciliary Body / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007498:Iris / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D000071841:PAX6 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D000071841:PAX6 Transcription Factor; C000605732:Pax6 protein, mouse
keywords: Aniridia; Downstream target; Iris; Pax6; Transcription factor