An important form of transcriptional gene regulation is alternative splicing (AS), the generation of several proteins from one gene. However, the identity of the RNA-binding proteins that control AS during development remains largely unknown. Now, Constance Cepko and co-workers reveal a temporal requirement for the AS factor Sfrs1, an arginine/serine-rich (SR) protein family member, in the survival of mouse retinal neurons (see ). They show that Sfrs1 is expressed in the developing mouse retina and is itself regulated by AS. The loss of Sfrs1 function during embryonic development, they report, causes the formation of small retinas that degenerate further after birth. Other experiments show that in the absence of Sfrs1, early-born retinal neurons are produced and begin differentiation, but then die through apoptosis; by contrast, late-born retinal neurons survive. The authors propose, therefore, that embryonically generated retinal neurons require Sfrs1-mediated alternative splicing for their terminal differentiation and/or maintenance, but postnatally generated neurons do not, thus highlighting a dynamic role for AS during development.
