The Smarce1 subunit of the BAF complex performs distinct, stage-specific functions during zebrafish retinal development

Abstract

In the developing vertebrate retina, progenitor cells proliferate and differentiate into specialized neurons with remarkable spatial and temporal precision. This process is coordinated by multiple interactions between the genome and the epigenome. Chromatin remodeling plays an important role in the regulation of retinal cell type specific transcriptional programs. Vertebrate switch/sucrose non-fermentable (SWI/SNF) complexes, also known as Brg1/Brg-associated factors (BAF complexes) are multi-subunit, ATP-dependent chromatin-remodeling complexes assembled from homologous subunit families. The ATPase subunit of these complexes, Smarca4 (also known as Brg1), has been implicated in retinal development. Among the other core subunits, one that is incorporated early into the BAF complex is Smarce1 (also known as Baf57), which is present in all BAF assemblies. Notably, recent findings show that this protein acts as a mitotic bookmark in mouse embryonic stem cells to preserve cell identity during cell division. In this work, we examined the retinal phenotype in smarce1 zebrafish mutants and compared it with that in smarca4 mouse and zebrafish mutants. The smarce1 gene was differentially expressed in progenitors and neurons during development. We found that Smarce1 deficiency reduces the cell proliferation of retinal progenitors and produces a severe cell death. Although all classes of retinal neurons are specified in smarce1 embryos, normal lamination of retinal cells is altered and differentiation of photoreceptors is deficient. Given that not all of these phenotypes are observed in the zebrafish smarca4/Brg1-mutant, we propose that a differential configuration of the BAF complex in the retina contributes to distinct functions during retinogenesis.