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Publication : The homeodomain transcription factor PITX2 is required for specifying correct cell fates and establishing angiogenic privilege in the developing cornea.

First Author  Gage PJ Year  2014
Journal  Dev Dyn Volume  243
Issue  11 Pages  1391-400
PubMed ID  25044936 Mgi Jnum  J:215601
Mgi Id  MGI:5605899 Doi  10.1002/dvdy.24165
Citation  Gage PJ, et al. (2014) The homeodomain transcription factor PITX2 is required for specifying correct cell fates and establishing angiogenic privilege in the developing cornea. Dev Dyn 243(11):1391-400
abstractText  BACKGROUND: Correct specification of cell lineages and establishing angiogenic privilege within the developing cornea are essential for normal vision but the mechanisms controlling these processes are poorly understood. RESULTS: We show that the homeodomain transcription factor PItX2 is expressed in mesenchymal cells of the developing and mature cornea and use a temporal gene knockout approach to demonstrate that PITX2 is required for corneal morphogenesis and the specification of cell fates within the surface ectoderm and mesenchymal primordia. PITX2 is also required to establish angiogenic privilege in the developing cornea. Further, the expression of Dkk2 and suppression of canonical Wnt signaling activity levels are key mechanisms by which PITX2 specifies ocular surface ectoderm as cornea. In contrast, specifying the underlying mesenchyme to corneal fates and establishing angiogenic privilege in the cornea are less sensitive to DKK2 activity. Finally, the cellular expression patterns of FOXC2, PITX1, and BARX2 in Pitx2 and Dkk2 mutants suggest that these transcription factors may be involved in specifying cell fate and establishing angiogenic privilege within the corneal mesenchyme. However, they are unlikely to play a role in specifying cell fate within the corneal ectoderm. CONCLUSIONS: Together, these data provide important insights into the mechanisms regulating cornea development. Developmental Dynamics 243:1391-1400, 2014. (c) 2014 Wiley Periodicals, Inc.
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