{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FJX1, the vertebrate homolog of the Drosophila protein Four‐jointed, is emerging as a multifunctional regulator involved in diverse processes including planar cell polarity (PCP), tissue morphogenesis, neuronal development, and tumorigenesis. Several studies demonstrate that FJX1 modulates PCP by interacting with Fat signaling components – for example, its repression by Fat4 and genetic interactions with other PCP genes affect oriented cell divisions and tubule elongation during kidney development, with dysregulation contributing to cystic kidney disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Complementary expression patterns of FJX1 with other PCP regulators in organs such as kidney, lung, and intestine further support its conserved role in tissue organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, FJX1 is a secreted protein whose expression is directly regulated by Notch signaling, suggesting it may act as a ligand to convey spatial and temporal cues during development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its role is not restricted to developmental processes; in the nervous system, FJX1 functions as an inhibitory factor that limits dendrite extension and branching in hippocampal neurons, thereby contributing to proper neuronal circuitry."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, aberrant FJX1 expression is implicated in pathological conditions. In models of renal injury and polycystic kidney disease, altered FJX1 levels are associated with enhanced fibrosis, inflammation, and cyst growth – changes that may be mediated via crosstalk between the PCP and Hippo signaling pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the context of cancer, elevated levels of FJX1 have been detected in several malignancies. For instance, in colon adenocarcinoma its upregulation functions in an oncogenic capacity and is regulated by microRNA networks, while in head and neck as well as oral squamous cell carcinomas FJX1 serves as an immunogenic target with potential for therapeutic vaccination"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, these studies collectively highlight FJX1 as a critical node that not only regulates developmental and polarity processes through its integration with PCP and Hippo pathways but also influences pathological outcomes in kidney disease and cancer. Its multifaceted roles and secreted nature offer promising avenues for biomarker development and targeted therapies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sakura Saburi, Ian Hester, Evelyne Fischer, et al. 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