Authors: Henrik Boije Henrik Ring Shahrzad Shirazi Fard Ida Grundberg Mats Nilsson Finn Hallböök
Publish Date: 2013/06/04
Volume: 51, Issue: 2, Pages: 615-628
Abstract
The proliferation cell cycle exit and differentiation of progenitor cells are controlled by several different factors The chromodomain protein mortality factor 4like 1 Morf4l1 has been ascribed a role in both proliferation and differentiation Little attention has been given to the existence of alternative splice variants of the Morf4l1 mRNA which encode two Morf41l isoforms a short isoform SMorf4l1 with an intact chromodomain and a long isoform LMorf4l1 with an insertion in or in the vicinity of the chromodomain The aim of this study was to investigate if this alternative splicing has a function during development We analysed the temporal and spatial distribution of the two mRNAs and overexpressed both isoforms in the developing retina The results showed that the SMorf4l1 mRNA is developmentally regulated Overexpression of SMorf4l1 using a retrovirus vector produced a clear phenotype with an increase of earlyborn neurons retinal ganglion cells horizontal cells and cone photoreceptor cells Overexpression of LMorf4l1 did not produce any distinguishable phenotype The overexpression of SMorf4l1 but not LMorf4l1 also increased apoptosis in the infected regions Our results suggest that the two Morf4l1 isoforms have different functions during retinogenesis and that Morf4l1 functions are finetuned by developmentally regulated alternative splicing The data also suggest that Morf4l1 contributes to the regulation of cell genesis in the retinaWe thank Karl Wahlin for the gatewayadapted RCAS vector Pernilla Bjerling for the discussions and input The work was supported by the Swedish Research Council 20859013 12187153 Barncancerfonden PROJ09/038 Ögonfonden St Eriks ögonsjukhus stipendier and Kronprinsessan Margaretas arbetsnämnd för synskadade
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