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The molecular basis of defective lens development in the Iberian mole.

Carmona FD, Jiménez R, Collinson JM - BMC Biol. (2008)

Bottom Line: Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development.PAX6 is not down-regulated 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.The undifferentiated status of the anterior epithelial cells was compromised, and most of them undergo apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. d.carmona@abdn.ac.uk

ABSTRACT

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 down-regulated 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 genes encoding beta-crystallins are not directly regulated by PAX6, c-MAF and PROX1 in the Iberian mole, as they are in other model vertebrates.

Conclusion: 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.

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Haematoxylin staining on mole wax sections. In the Iberian mole, the lens placode is established at the end of the s3 stage, that is, about 13 days post-coitum (dpc) and it rapidly invaginates forming the lens pit (s4a, 14 dpc). At s5a (17 dpc), the lens is clearly polarised and the posterior cells have already begun to elongate. About 5 days later (s7, about 22 dpc), lens fibre cells have not reached the centre of the lens epithelium (arrow). Lens occlusion has not been completed at the last prenatal stage (s8, about 26 dpc), as a small lens cavity is still observed (arrow). After birth, several vacuoles in the epithelium/fibre cells boundary (arrowheads) are seen in the lens of newborn moles (s9, 1 day post-partum), a situation maintained until adulthood (not shown). Scale bar represents 100 μm in all figures.
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Figure 3: Haematoxylin staining on mole wax sections. In the Iberian mole, the lens placode is established at the end of the s3 stage, that is, about 13 days post-coitum (dpc) and it rapidly invaginates forming the lens pit (s4a, 14 dpc). At s5a (17 dpc), the lens is clearly polarised and the posterior cells have already begun to elongate. About 5 days later (s7, about 22 dpc), lens fibre cells have not reached the centre of the lens epithelium (arrow). Lens occlusion has not been completed at the last prenatal stage (s8, about 26 dpc), as a small lens cavity is still observed (arrow). After birth, several vacuoles in the epithelium/fibre cells boundary (arrowheads) are seen in the lens of newborn moles (s9, 1 day post-partum), a situation maintained until adulthood (not shown). Scale bar represents 100 μm in all figures.

Mentions: Haematoxylin staining of tissue sections showed that the mole lens begins to develop properly. The lens vesicle detaches completely from the overlying surface ectoderm and become polarised (Figure 3). However, important differences were found in relation to mouse lenses at similar stages. One difference is that a conspicuous lens cavity is observed until the last prenatal stage, that is, s8, 24–28 days post-coitum (dpc). This means that lens occlusion lasts around 10 days. Primary lens fibre elongation is very slow in moles compared with mice, in which this process only takes 2 days (from 11.5 to 13.5 dpc; [39]). Furthermore, several vacuoles appeared in the epithelium-lens fibres borderline at the s9 stage (newborn moles) and remained there even in adulthood, unlike mouse lenses.


The molecular basis of defective lens development in the Iberian mole.

Carmona FD, Jiménez R, Collinson JM - BMC Biol. (2008)

Haematoxylin staining on mole wax sections. In the Iberian mole, the lens placode is established at the end of the s3 stage, that is, about 13 days post-coitum (dpc) and it rapidly invaginates forming the lens pit (s4a, 14 dpc). At s5a (17 dpc), the lens is clearly polarised and the posterior cells have already begun to elongate. About 5 days later (s7, about 22 dpc), lens fibre cells have not reached the centre of the lens epithelium (arrow). Lens occlusion has not been completed at the last prenatal stage (s8, about 26 dpc), as a small lens cavity is still observed (arrow). After birth, several vacuoles in the epithelium/fibre cells boundary (arrowheads) are seen in the lens of newborn moles (s9, 1 day post-partum), a situation maintained until adulthood (not shown). Scale bar represents 100 μm in all figures.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2587461&req=5

Figure 3: Haematoxylin staining on mole wax sections. In the Iberian mole, the lens placode is established at the end of the s3 stage, that is, about 13 days post-coitum (dpc) and it rapidly invaginates forming the lens pit (s4a, 14 dpc). At s5a (17 dpc), the lens is clearly polarised and the posterior cells have already begun to elongate. About 5 days later (s7, about 22 dpc), lens fibre cells have not reached the centre of the lens epithelium (arrow). Lens occlusion has not been completed at the last prenatal stage (s8, about 26 dpc), as a small lens cavity is still observed (arrow). After birth, several vacuoles in the epithelium/fibre cells boundary (arrowheads) are seen in the lens of newborn moles (s9, 1 day post-partum), a situation maintained until adulthood (not shown). Scale bar represents 100 μm in all figures.
Mentions: Haematoxylin staining of tissue sections showed that the mole lens begins to develop properly. The lens vesicle detaches completely from the overlying surface ectoderm and become polarised (Figure 3). However, important differences were found in relation to mouse lenses at similar stages. One difference is that a conspicuous lens cavity is observed until the last prenatal stage, that is, s8, 24–28 days post-coitum (dpc). This means that lens occlusion lasts around 10 days. Primary lens fibre elongation is very slow in moles compared with mice, in which this process only takes 2 days (from 11.5 to 13.5 dpc; [39]). Furthermore, several vacuoles appeared in the epithelium-lens fibres borderline at the s9 stage (newborn moles) and remained there even in adulthood, unlike mouse lenses.

Bottom Line: Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development.PAX6 is not down-regulated 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.The undifferentiated status of the anterior epithelial cells was compromised, and most of them undergo apoptosis.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. d.carmona@abdn.ac.uk

ABSTRACT

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 down-regulated 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 genes encoding beta-crystallins are not directly regulated by PAX6, c-MAF and PROX1 in the Iberian mole, as they are in other model vertebrates.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus