PuSH - Publication Server of Helmholtz Zentrum München

Ahmad, N. ; Aslam, M. ; Münster, D. ; Horsch, M. ; Khan, M.A. ; Carlsson, P.* ; Beckers, J. ; Graw, J.

Pitx3 directly regulates Foxe3 during early lens development.

Int. J. Dev. Biol. 57, 741-751 (2013)
Publ. Version/Full Text Volltext DOI PMC
Closed
Open Access Green as soon as Postprint is submitted to ZB.
Pitx3 is a bicoid-related homeodomain transcription factor critical for the development of the ocular lens, mesencephalic dopaminergic neurons and skeletal muscle. In humans, mutations in PITX3 are responsible for cataracts and anterior segment abnormalities of varying degree; polymorphisms are associated with Parkinson’s disease. In aphakia (ak) mice, two deletions in the promoter region of Pitx3 cause abnormal lens development. Here, we investigated systematically the role of Pitx3 in lens development including its molecular targets responsible for the ak phenotype. We have shown that ak lenses exhibit reduced proliferation and aberrant fiber cell differentiation. This was associated with loss of Foxe3 expression, complete absence of Prox1 expression, reduced expression of epsilon-tubulin and earlier expression of gamma-crystallin during lens development. Using EMSA and ChIP assays, we demonstrated that Pitx3 binds to an evolutionary conserved bicoid-binding site on the 5’-upstream region of Foxe3. Finally, Pitx3 binding to 5’-upstream region of Foxe3 increased transcriptional activity significantly in a cell-based reporter assay. Identification of Foxe3 as a transcriptional target of Pitx3 explains at least in part some of the phenotypic similarities of the ak and dyl mice (dysgenic lens, a Foxe3 allele). These findings enhance our understanding of the molecular cascades which subserve lens development.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Pitx3; aphakia; lens development; Prox1; Foxe3; Ap-2-alpha Transcription Factor; Cell-cell-adhesion; Gene-expression; E-cadherin; Dopaminergic-neurons; Vesicle Separation; Anterior Segment; Epsilon-tubulin; Eye Development; Homeobox Gene
ISSN (print) / ISBN 0214-6282
e-ISSN 1696-3547
Journal International Journal of Developmental Biology
Quellenangaben Volume: 57, Issue: 9-10, Pages: 741-751 Article Number: , Supplement: ,
Publisher University of the Basque Country Press (UBC Press)
Publishing Place Bilbao
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)