{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSeveral studies have highlighted the diverse roles played by proteins involved in reproductive and developmental processes. For example, investigations into Tudor‐domain–containing proteins, such as STK31/TDRD8, have revealed their critical roles in the assembly of nuage-associated granules and in regulating spermatogenesis in mice, illustrating complex mechanisms in germ cell development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, CIROP—a putative extracellular metallopeptide protease—is expressed exclusively in ciliated left–right organizers (LROs) during vertebrate embryogenesis. Functional studies in zebrafish and Xenopus have demonstrated that CIROP operates solely on the left side: it acts downstream of the leftward flow generated by motile cilia yet upstream of the asymmetric expression of DAND5. This precise positioning within the developmental cascade is critical for establishing left–right asymmetry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, human genetic data indicate that loss-of-function mutations in CIROP result in recessive situs anomalies, reinforcing its essential role in left–right patterning. Collectively, these findings suggest that CIROP is an integral component of an ancestral genetic module that, despite being lost in certain vertebrate lineages, remains indispensable for proper left–right axis determination in humans."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jianqiang Bao, Li Wang, Jianbo Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STK31(TDRD8) is dynamically regulated throughout mouse spermatogenesis and interacts with MIWI protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00418-011-0897-9"}], "href": "https://doi.org/10.1007/s00418-011-0897-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22205278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22205278"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jian Zhou, N Adrian Leu, Sigrid Eckardt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STK31/TDRD8, a germ cell-specific factor, is dispensable for reproduction in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0089471"}], "href": "https://doi.org/10.1371/journal.pone.0089471"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24586802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24586802"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Emmanuelle Szenker-Ravi, Tim Ott, Muznah Khatoo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41588-021-00970-4"}], "href": "https://doi.org/10.1038/s41588-021-00970-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34903892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34903892"}]}]}]}