Roles of Zfp36l1 and Zfp36l1 in retinal development

We report our study of the function of two members of the TTP (tristetraprolin) mRNA binding protein family, Zfp36l1 and Zfp36l2, in retinal development. We found that Zfp36l1 and Zfp36l2 were expressed in retinal progenitor cells during development and Müller glial cells and photoreceptors in the mature retina. Our analysis of the mutant retinas showed that, whereas the single knockout retinas appeared largely normal, the double knockout (DKO) retina manifested decreased RPC proliferation and increased differentiation of multiple retinal cell types. RNA-seq analysis not only confirmed the imbalance of proliferation and differentiation in the DKO retina but also revealed Zfp36l1 and Zfp36l2 interact with multiple signaling pathways including the sonic hedgehog pathway and the Notch pathway, to regulate this process. Zfp36l1 and Zfp36l2 were conditionally knocked out by crossing two floxed alleles (Zfp36l1F and Zfp36l2F) with the retinal specific Cre line Vsx2-Cre. Transcriptomic profiles of the double knockout (Zfp36l1/F/F;Zfp36l2F/F; Vsx2-Cre) retina and control retina (Zfp36l1/F/F;Zfp36l2F/F) from different stages (E14.5, E17.5, P0, P5 and P16) were compared by RNA-seq.