The molecular basis of defective lens development in the Iberian Mole

DSCN3983.JPGThe molecular basis of defective lens development in the Iberian Mole

Francisco DAVID Carmona , Rafael Jimenez and Jon MARTIN Collinson

BMC Biology 2008, 6:44doi:10.1186/1741-7007-6-44


Background
Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development. We have studied eye development in a species of true mole, the Iberian mole Talpa occidentalis, and present the molecular basis of abnormal lens development. This is the first embryological developmental study of the eyes of any fossorial mammal at the molecular level.

Results
Lens fibre differentiation is not completed in the Iberian mole. Although eye development starts normally (similar to other model species), defects are seen after closure of the lens vesicle. PAX6 is not downregulated in developing lens fibre nuclei, as it is in other species, and there is ectopic expression of FOXE3, a putative downstream effector of PAX6, in some but not all lens fibres. FOXE3-positive lens fibres continue to proliferate within the posterior compartment of the embryonic lens, but unlike in the mouse, no proliferation was detected anywhere in the postnatal mole lens. The undifferentiated status of the anterior epithelial cells was compromised, and most of them undergo apoptosis. Furthermore, beta-crystallin and PROX1 expression patterns are abnormal and our data suggest that beta-crystallin genes are not directly regulated by PAX6, c-MAF and PROX1 in Talpa occidentalis, as they are in other model vertebrates.

Conclusions
In other model vertebrates, genetic pathways controlling lens development robustly compartmentalise the lens into a simple, undifferentiated, proliferative anterior epithelium, and quiescent, anuclear, terminally differentiated posterior lens fibres. These pathways are not as robust in the mole, and lead to loss of the anterior epithelial phenotype and only partial differentiation of the lens fibres, which continue to express ‘epithelial’ genes. Paradigms of genetic regulatory networks developed in other vertebrates appear not to hold true for the Iberian mole.

crédit photo, page de Dr Martin Collinson

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