April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Replacement of Math5 by Hes1 Resulted in Cell Cycle Reentry
Author Affiliations & Notes
  • S. W. Wang
    Ophthal & Visual Science, Univ of Texas Medical School, Houston, Texas
  • D. Yangirova
    Rice University, Houston, Texas
  • Footnotes
    Commercial Relationships  S.W. Wang, None; D. Yangirova, None.
  • Footnotes
    Support  E. Matilda Ziegler Foundation for the Blind, Herman Eye Fund.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2525. doi:
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      S. W. Wang, D. Yangirova; Replacement of Math5 by Hes1 Resulted in Cell Cycle Reentry. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2525.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Notch pathway plays a pivotal role in regulating the cell number by maintaining the progenitor pool in the retina. Its action is, in a large part, conducted through the downstream effector Hes1, which inhibits activation of proneural genes. Upon lifting of Hes1 inhibition, math5 (atoh7) is the first to be activated. Activation of math5 leads to specification of retinal ganglion cells and, likely, other early retinal cell types. We want to know whether Hes1 can push the differentiating precursor cells, which have already exited the cell cycle, back into their cell cycle.

Methods: : We generated a math5hes1/hes1 mouse line in which the math5 coding sequence was replaced by a hes1 cDNA. The math5hes1/hes1 and math5hes1/+ retinas were analyzed at various developmental stages. Wildtype and math5-/- retinas were used as controls. Numbers of proliferating and apoptotic cells were assayed. Total retinal cell number and the numbers of specific retinal cell types were also estimated.

Results: : We found that the math5hes1/hes1 retina was hyper-proliferative during early retinogenetic stages and hypo-proliferative during late retinogenetic stages. The math5hes1/hes1 Retina contained more cells at the early stages when compared to wildtype and math5-/- retinas. However, the adult math5hes1/hes1 retina had the highest total cell loss that we have ever observed. The cell loss was clearly due excess amount of apoptosis.

Conclusions: : Our results indicate that the Notch downstream effector Hes1 is able to push differentiating cells back to cell cycle. However, these cells may not differentiate properly in a late retinal environment and, therefore, undergo apoptosis which resulting a vastly abnormal retina.

Keywords: retinal development • proliferation • retinal glia 

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