TY  - JOUR
TI  - Pitx3 directly regulates <I>Foxe3</I> during early lens development
AU  - Ahmad, Nafees
AU  - Aslam, Muhammad
AU  - Muenster, Doris
AU  - Horsch, Marion
AU  - Khan, MuhammadA.
AU  - Carlsson, Peter
AU  - Beckers, Johannes
AU  - Graw, Jochen
T2  - The International Journal of Developmental Biology
AB  - 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. 
PY  - 2013
DO  - 10.1387/ijdb.130193jg
VL  - 57
IS  - 9-10
SP  - 741
EP  - 751
J2  - Int. J. Dev. Biol.
LA  - en
SN  - 0214-6282
SN  - 1696-3547
UR  - https://ijdb.ehu.eus/article/130193jg
Y2  - 2024/11/05/13:16:08
ER  -