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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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Spatiotemporal expression pattern of PROX1 in the Iberian mole lens. In mouse samples (E12, E18), specific Prox1-immunofluorescence is observed in the nucleus of differentiating lens fibres and in the cytoplasm of epithelial cells. During the mole lens development, PROX1 showed a cytoplasmic distribution in the invaginating lens placode (s4a). Once the lens vesicle becomes polarised, PROX1 is highly detected in the nucleus of all the lens cells (s5a, s5c). From the s6 stage on, cytoplasmic localisation of PROX1 is clearly seen mainly in posterior fibre cells but also in the lens epithelium. Photomicrographs were taken using a single bandpass fluorescence mirror unit and merged with 'The Gimp' software. Scale bar represents 100 μm in all figures. LE, lens epithelium; FC, fibre cells; LP, lens pit.
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Figure 6: Spatiotemporal expression pattern of PROX1 in the Iberian mole lens. In mouse samples (E12, E18), specific Prox1-immunofluorescence is observed in the nucleus of differentiating lens fibres and in the cytoplasm of epithelial cells. During the mole lens development, PROX1 showed a cytoplasmic distribution in the invaginating lens placode (s4a). Once the lens vesicle becomes polarised, PROX1 is highly detected in the nucleus of all the lens cells (s5a, s5c). From the s6 stage on, cytoplasmic localisation of PROX1 is clearly seen mainly in posterior fibre cells but also in the lens epithelium. Photomicrographs were taken using a single bandpass fluorescence mirror unit and merged with 'The Gimp' software. Scale bar represents 100 μm in all figures. LE, lens epithelium; FC, fibre cells; LP, lens pit.

Mentions: PROX1 and c-MAF play important roles in lens fibre differentiation [16]. In the mouse lens, Prox1 is primarily detected in the nuclei of the differentiating lens fibres but in the cytoplasm of the lens epithelial cells (mouse rows in Figure 6; [40]). The spatiotemporal expression pattern of PROX1 in the lens of the Iberian mole clearly differs from that observed in mouse. In the mole, PROX1 was detected in the cytoplasm of the cells forming the invaginating lens placode at the s3 stage (Figure 6). During primary lens fibre differentiation, both epithelial and fibre cell nuclei expressed PROX1. A clear increase in cytoplasmic PROX1-immunoreactivity was observed from stage s6 (mainly in the lens fibres), although the main signal was in the nuclei (Figure 6, last row). This weaker cytoplasmic expression was maintained until adulthood. In postnatal stages, including the adult, some fibre cell nuclei appeared less PROX1-immunoreactive (not shown), and the fluorescence was barely detectable in some nuclei.


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

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

Spatiotemporal expression pattern of PROX1 in the Iberian mole lens. In mouse samples (E12, E18), specific Prox1-immunofluorescence is observed in the nucleus of differentiating lens fibres and in the cytoplasm of epithelial cells. During the mole lens development, PROX1 showed a cytoplasmic distribution in the invaginating lens placode (s4a). Once the lens vesicle becomes polarised, PROX1 is highly detected in the nucleus of all the lens cells (s5a, s5c). From the s6 stage on, cytoplasmic localisation of PROX1 is clearly seen mainly in posterior fibre cells but also in the lens epithelium. Photomicrographs were taken using a single bandpass fluorescence mirror unit and merged with 'The Gimp' software. Scale bar represents 100 μm in all figures. LE, lens epithelium; FC, fibre cells; LP, lens pit.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Spatiotemporal expression pattern of PROX1 in the Iberian mole lens. In mouse samples (E12, E18), specific Prox1-immunofluorescence is observed in the nucleus of differentiating lens fibres and in the cytoplasm of epithelial cells. During the mole lens development, PROX1 showed a cytoplasmic distribution in the invaginating lens placode (s4a). Once the lens vesicle becomes polarised, PROX1 is highly detected in the nucleus of all the lens cells (s5a, s5c). From the s6 stage on, cytoplasmic localisation of PROX1 is clearly seen mainly in posterior fibre cells but also in the lens epithelium. Photomicrographs were taken using a single bandpass fluorescence mirror unit and merged with 'The Gimp' software. Scale bar represents 100 μm in all figures. LE, lens epithelium; FC, fibre cells; LP, lens pit.
Mentions: PROX1 and c-MAF play important roles in lens fibre differentiation [16]. In the mouse lens, Prox1 is primarily detected in the nuclei of the differentiating lens fibres but in the cytoplasm of the lens epithelial cells (mouse rows in Figure 6; [40]). The spatiotemporal expression pattern of PROX1 in the lens of the Iberian mole clearly differs from that observed in mouse. In the mole, PROX1 was detected in the cytoplasm of the cells forming the invaginating lens placode at the s3 stage (Figure 6). During primary lens fibre differentiation, both epithelial and fibre cell nuclei expressed PROX1. A clear increase in cytoplasmic PROX1-immunoreactivity was observed from stage s6 (mainly in the lens fibres), although the main signal was in the nuclei (Figure 6, last row). This weaker cytoplasmic expression was maintained until adulthood. In postnatal stages, including the adult, some fibre cell nuclei appeared less PROX1-immunoreactive (not shown), and the fluorescence was barely detectable in some nuclei.

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