Shroom3, a member of the SHROOM protein family, is unique as it regulates actin dynamics via apical constriction and apicobasal cell elongation. It is involved in multiple biological processes, with its function linked to the planar cell polarity pathway and playing a role in epithelial morphogenesis [1,4]. Genetic models, especially knockout mouse models, are valuable for studying Shroom3.

In kidney-related studies, Shroom3 heterozygous null mice (Shroom3Gt/+) showed higher mortality, worsened kidney function, and disrupted epithelial redifferentiation after ischemic injury, indicating its role in epithelial repair and redifferentiation in the kidney [3]. In optic cup development, Shroom3 deficiency in mouse embryos led to coloboma phenotypes due to disrupted tissue alignment and failure to re-establish apical-basal polarity during epithelial fusion [2]. In cardiac development, Shroom3gt/gt mice exhibited congenital heart defects, suggesting its function as an actomyosin cytoskeleton effector downstream of the planar cell polarity signaling pathway [4].

In conclusion, Shroom3 is essential for epithelial morphogenesis, playing significant roles in kidney development, optic cup morphogenesis, and cardiac development. Studies using Shroom3 knockout mouse models have revealed its functions in these processes and provided insights into related diseases such as chronic kidney disease, ocular coloboma, and congenital heart defects [1-3,6].

References:

1. Paul, Amy, Lawlor, Allison, Cunanan, Kristina, Lanktree, Matthew B, Bridgewater, Darren. 2023. The Good and the Bad of SHROOM3 in Kidney Development and Disease: A Narrative Review. In Canadian journal of kidney health and disease, 10, 20543581231212038. doi:10.1177/20543581231212038. https://pubmed.ncbi.nlm.nih.gov/38107159/

2. Herstine, Jessica A, Mensh, Jordyn, Coffman, Electra, Bridgewater, Darren, Plageman, Timothy F. 2025. Shroom3 facilitates optic fissure closure via tissue alignment and reestablishment of apical-basal polarity during epithelial fusion. In Developmental biology, 522, 91-105. doi:10.1016/j.ydbio.2025.03.008. https://pubmed.ncbi.nlm.nih.gov/40113025/

3. Li, Aihua, Cunanan, Joanna, Khalili, Hadiseh, Drysdale, Thomas, Bridgewater, Darren. 2021. Shroom3, a Gene Associated with CKD, Modulates Epithelial Recovery after AKI. In Kidney360, 3, 51-62. doi:10.34067/KID.0003802021. https://pubmed.ncbi.nlm.nih.gov/35368578/

4. Durbin, Matthew D, O'Kane, James, Lorentz, Samuel, Firulli, Anthony B, Ware, Stephanie M. 2020. SHROOM3 is downstream of the planar cell polarity pathway and loss-of-function results in congenital heart defects. In Developmental biology, 464, 124-136. doi:10.1016/j.ydbio.2020.05.013. https://pubmed.ncbi.nlm.nih.gov/32511952/