Signals from the lens and Foxc1 regulate the expression of key genes during the onset of corneal endothelial development.
Correct formation of the corneal endothelium is essential for continued development of the anterior segment of the eye. Corneal endothelial development is initiated at E12 when precursor peri-ocular mesenchyme cells migrate into the space between the lens and the presumptive corneal epithelium and begin to respond to signals from the lens, undergoing a mesenchymal to epithelial transition (MET) that is complete by E15.5. To study the initiation of MET, peri-ocular mesenchyme cell lines were derived from E12.5 and E13.5 murine embryos. These cells expressed key transcription factors, Foxc1 and Pitx2, as well as Slug and Tsc22, genes involved in MET. We have shown that all these genes must be down-regulated by E13.5 for differentiation to proceed. Lens-derived signals play a role in this down-regulation with Tgfβ2 specifically down-regulating Foxc1 and Pitx2. Over-expression and knock-down of Foxc1 significantly and similarly affected the expression of Pitx2, Tsc22 and Slug while Foxc1 was shown to play a role in mediating the lens effects on Slug. Thus, for the progression of initial corneal endothelial development, the key transcription factors, Foxc1 and Pitx2, as well as genes involved in MET, Slug and Tsc-22, must be down-regulated, a process driven by the lens and Foxc1.
School of Life Sciences, University of KwaZulu-Natal Westville Campus, Durban 4001, South Africa.
Zenzele T V
ZT
Silla
School of Life Sciences, University of KwaZulu-Natal Westville Campus, Durban 4001, South Africa.
Jerolen
J
Naidoo
Department of Human Biology, University of Cape Town Medical School, Anzio Road, Observatory, South Africa.
Susan H
SH
Kidson
School of Life Sciences, University of KwaZulu-Natal Westville Campus, Durban 4001, South Africa. Electronic address: sommerp@ukzn.ac.za.
Paula
P
Sommer
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D002645:Chickens; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004728:Endothelium, Corneal / Q000166:cytology* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D000097577:Homeobox Protein PITX2
D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053781:Transforming Growth Factor beta2; D000097577:Homeobox Protein PITX2; C112890:Foxc1 protein, mouse; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; C509042:Tgfb2 protein, mouse
Corneal endothelial development; Foxc1; Lens; Peri-ocular mesenchyme; Pitx2