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Dmitri Serjanov, Galina Bachay, Dale D Hunter, William J Brunken; Laminin β2 and γ3 Chains Regulate Retinal Progenitor Cell Division Polarity. Invest. Ophthalmol. Vis. Sci. 2014;55(13):711.
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© ARVO (1962-2015); The Authors (2016-present)
Basement membranes are highly organized extracellular matrices that are important sources of developmental cues. Laminin, a heterotrimeric molecule, is an indispensable organizational component of basement membranes. Mutations in laminin genes lead to defective CNS and ocular development in mice and humans. This study investigates the role of two constituents of CNS laminins, laminin β2 and γ3 chains in the regulation of the retinal progenitor cell polarity as characterized by angles of division, cell cycle dynamics and the consequent neurogenesis.
Retinae from P3 WT, laminin β2-/- and laminin γ3-/- mice were used in this study. Immunohistochemistry was performed using centrosomal and mitotic markers. Retinal progenitor cell angles of division were visualized through 3D-reconstruction of the dividing nuclei. Division angles were calculated in 3D by measuring the angle between a line joining opposing centrosomes and the plane of the apical retinal surface.
It has been previously shown that deletion of the laminin β2 and γ3 chains results in alteration of the cell cycle of retinal progenitor cells, retinal ganglion cell development, Müller glial cell polarity and photoreceptor development. Here, we demonstrate different cell division dynamics between developmentally older and younger regions of the retina as well as a disruption in laminin mutants. In WT retinae, cell divisions in younger regions are preferentially symmetrical and gradually become more asymmetric as the retina becomes older. In laminin β2-/-retinae, the divisions in all regions are skewed, with noticeable division abnormalities. In laminin γ3-/- retinae, younger regions are unaffected, whereas older regions are more symmetrically oriented than in WT retinae. There is also a high incidence of centrosomal abnormalities in laminin β2-/-retinae, such as multipolar cells and centrosomes with multiple centrioles.
Together with our previous findings, these data suggest that the ILM provides orientation cues and that laminin deletions lead to premature progenitor pool depletion, resulting in overproduction of early-born cells at the expense of later-born ones.
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