title: Alternative splicing of the chromodomain protein Morf4l1 pre-mRNA has implications on cell differentiation in the developing chicken retina.
abstract: The proliferation, cell cycle exit and differentiation of progenitor cells are controlled by several different factors. The chromodomain protein mortality factor 4-like 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 (S-Morf4l1) with an intact chromodomain and a long isoform (L-Morf4l1) 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 over-expressed both isoforms in the developing retina. The results showed that the S-Morf4l1 mRNA is developmentally regulated. Over-expression of S-Morf4l1 using a retrovirus vector produced a clear phenotype with an increase of early-born neurons: retinal ganglion cells, horizontal cells and cone photoreceptor cells. Over-expression of L-Morf4l1 did not produce any distinguishable phenotype. The over-expression of S-Morf4l1 but not L-Morf4l1 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 fine-tuned by developmentally regulated alternative splicing. The data also suggest that Morf4l1 contributes to the regulation of cell genesis in the retina.
authors.affiliation: Department of Neuroscience, BMC, Uppsala University, Box 593, Biomedical Center, 75124, Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Boije
authors.forename: Henrik
authors.initials: H
authors.lastname: Ring
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Shirazi Fard
authors.forename: Ida
authors.initials: I
authors.lastname: Grundberg
authors.forename: Mats
authors.initials: M
authors.lastname: Nilsson
authors.forename: Finn
authors.initials: F
authors.lastname: Hallböök
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D014157:Transcription Factors