title: The guanine nucleotide exchange factor Vav3 regulates differentiation of progenitor cells in the developing mouse retina.
abstract: The seven main cell types in the mammalian retina arise from multipotent retinal progenitor cells, a process that is tightly regulated by intrinsic and extrinsic signals. However, the molecular mechanisms that control proliferation, differentiation and cell-fate decisions of retinal progenitor cells are not fully understood yet. Here, we report that the guanine nucleotide exchange factor Vav3, a regulator of Rho-GTPases, is involved in retinal development. We demonstrate that Vav3 is expressed in the mouse retina during the embryonic period. In order to study the role of Vav3 in the developing retina, we generate Vav3-deficient mice. The loss of Vav3 results in an accelerated differentiation of retinal ganglion cells and cone photoreceptors during early and late embryonic development. We provide evidence that more retinal progenitor cells express the late progenitor marker Sox9 in Vav3-deficient mice than in wild-types. This premature differentiation is compensated during the postnatal period and late-born cell types such as bipolar cells and Müller glia display normal numbers. Taken together, our data imply that Vav3 is a regulator of retinal progenitor cell differentiation, thus highlighting a novel role for guanine nucleotide exchange factors in retinogenesis.
authors.affiliation: Department of Cell Morphology & Molecular Neurobiology, Ruhr-University Bochum, NDEF 05/594 Universitaetsstrasse 150, 44780, Bochum, Germany.|International Graduate School of Neuroscience (IGSN), FNO 1/116 Universitaetsstrasse 150, 44780, Bochum, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Luft
authors.affiliation: Department of Cell Morphology & Molecular Neurobiology, Ruhr-University Bochum, NDEF 05/594 Universitaetsstrasse 150, 44780, Bochum, Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Reinhard
authors.affiliation: Division of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Masabumi
authors.initials: M
authors.lastname: Shibuya
authors.affiliation: Institute of Biochemistry and Cell Biology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Fischer
authors.affiliation: Department of Cell Morphology & Molecular Neurobiology, Ruhr-University Bochum, NDEF 05/594 Universitaetsstrasse 150, 44780, Bochum, Germany. Andreas.Faissner@ruhr-uni-bochum.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Faissner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D047108:Embryonic Development; D018390:Gene Targeting; D018345:Mice, Knockout; D008954:Models, Biological; D051567:Proto-Oncogene Proteins c-vav / Q000172:deficiency / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C496622:Vav3 protein, mouse