Temporal requirement of the alternative-splicing factor Sfrs1 for the survival of retinal neurons.
Alternative splicing is the primary mechanism by which a limited number of protein-coding genes can generate proteome diversity. We have investigated the role of the alternative-splicing factor Sfrs1, an arginine/serine-rich (SR) protein family member, during mouse retinal development. Loss of Sfrs1 function during embryonic retinal development had a profound effect, leading to a small retina at birth. In addition, the retina underwent further degeneration in the postnatal period. Loss of Sfrs1 function resulted in the death of retinal neurons that were born during early to mid-embryonic development. Ganglion cells, cone photoreceptors, horizontal cells and amacrine cells were produced and initiated differentiation. However, these neurons subsequently underwent cell death through apoptosis. By contrast, Sfrs1 was not required for the survival of the neurons generated later, including later-born amacrine cells, rod photoreceptors, bipolar cells and Müller glia. Our results highlight the requirement of Sfrs1-mediated alternative splicing for the survival of retinal neurons, with sensitivity defined by the window of time in which the neuron was generated.
Kanadia
Rahul N
RN
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Clark
Victoria E
VE
Punzo
Claudio
C
Trimarchi
Jeffrey M
JM
Cepko
Constance L
CL
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D047108:Embryonic Development / Q000235:genetics; D005124:Eye Abnormalities / Q000196:embryology / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D055351:Retinal Neurons / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D000068103:Serine-Arginine Splicing Factors; D013997:Time Factors
D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors