Российская академия наук


THE MOLECULAR BASIS OF NEUROGENESIS IN THE VERTEBRATE RETINA DEVELOPMENT AND REGENERATION



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THE MOLECULAR BASIS OF NEUROGENESIS IN THE VERTEBRATE RETINA DEVELOPMENT AND REGENERATION

Yu.V. Markitantova, P.P. Avdonin, R.D. Zinovieva, E.N. Grygoryan

Koltsov Institute of Developmental Biology Russian Academy of Science, Moscow, Russia, yuliya.mark@gmail.com


The study of molecular-genetic mechanisms of retina neurogenesis is one of the central areas of biology and medicine. Developing retina of the higher vertebrates and regenerating retina of lower vertebrates (newts) serve as the models for the study of cell-cell interactions, cell migration, proliferation, differentiation and finding ways to stimulate regeneration in human. Retina regeneration from the retinal pigment epithelial cells with the restoration of visual function has reached advanced level in the newts and typical for them at any age. But in higher vertebrates retina regeneration is possible only on the early stages of embryogenesis and lost in adulthood. Differentiated retinal pigment epithelial cells dedifferentiate after complete retina removal in the newt and form a population of

multipotent neuroblasts that give rise to the neurons and glial cells during retina recovering. The period of neuroblasts occurs, as in the development and regeneration of eye retina. We studied the expression pattern of key regulatory and signaling genes (eye field transcription factors (EFTFs) - Pax6, Prox1, Six3, Pitx1, 2, Fgf2, Tgfb2 in the human retina during prenatal development and in the adult newt retina at successive stages of regeneration. We used the methods of histology, molecular biology (PCR) and immunohistochemistry (proteins localization on eye сryosections, Western-blot). We found the expression of genes Pax6, Prox1, Six3, Pitx1, 2, Fgf2, Tgfb2 in both of the models, from the stage of neuroblasts which are characterized by active proliferation. Investigated regulatory factors are expressed in differentiating cells of developing human retina and also in the newt retina throughout the period of recovery. The regulatory genes Pax6, Prox1, Six3, Pitx1, 2, Fgf2, Tgfb2 take part in the formation of a specific molecular profile of retinal neurons. Thus, despite the differences in the origin of neuroblasts during retina development from neuroectoderm cells and regeneration from pigment epithelium cells, the program of retina neurogenesis in both processes is controlled by a similar set of regulatory factors.



This work was supported by RFFR (grant № 11-04-00728; 11-04-00125), Program Presidium of Russian Academy of Science “The dynamics of gene pools conservation”.

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