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Subcellular localization

Ciliary associated gene, Nucleoplasm

Functional category

• Small GTPases

Function

To investigate the role of chromatin remodeling complexes in ciliary regulation and embryonic development, we performed a targeted morpholino (MO)-based knockdown screen of 25 genes encoding core subunits of the 4 major ATP-dependent chromatin-remodeling families. This screen included 10 genes encoding SWI/SNF components (brg1/smarca4a, brm/smarca2, baf250/arid1ab, smarcc1a, arid2, baf57/smarce1, baf60a/smarcd1, baf53a/actl6a, snf5/smarcb1a, and brd7), 3 encoding ISWI components (smarca5, baz1a, and chrac1), 10 encoding CHD components (chd2, chd4a, chd4b, chd7, mta2, mta3, hdac1, parp1, rbbp4, and mbd3a), and 2 encoding INO80 components (ino80 and srcap). Notably, knocking down five of these SWI/SNF genes resulted in cilia-related phenotypes, such as body curvature, kidney cysts, and retina degeneration (Fig. S1A). Using CRISPR/Cas9 technology, we generated mutants for the three genes with the highest incidence of cystic kidneys upon knockdown: smarca4a, smarce1, and actl6a. Mutations in these three genes led to cystic kidneys or pericardial edema (Figs. 1B, 1C, S1B). As the smarca4a−/− and smarce1−/− mutants exhibited only mild cystic kidney phenotypes, we speculated that the effects were masked by maternally supplied gene products. Our genetic screen has identified several key subunits, including Smarca4a/Brg1, Smarce1, Smarca2, Actl6a, and Smarcb1a, as essential for kidney development, likely through their shared role in maintaining cilia stability(41213452).