{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Adenomatosis polyposis coli down‐regulated 1 (APCDD1) has emerged as a multifunctional component within the Wnt/β‑catenin signaling network. Initially identified as a transcriptional target of Wnt/β‑catenin in cancer cell lines and developing mouse embryos, APCDD1 exhibits a distinct spatiotemporal expression pattern in extraembryonic tissues, the nervous system, vascular structures, and regions undergoing critical epithelio‐mesenchymal interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, a methylated DNA region located between the VAPA and APCDD1 genes has been exploited as an epigenetic biomarker for noninvasive prenatal detection of chromosomal aneuploidies, underscoring its diagnostic utility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Functionally, APCDD1 acts as an inhibitor of canonical Wnt signaling. In adipose tissues, for example, upregulation of APCDD1 in mature adipocytes is associated with the repression of Wnt pathway expression and promotes adipogenic differentiation, whereas reduced APCDD1 expression in the context of diet‐induced obesity correlates with impaired adipogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " During tooth development, APCDD1 modulates the expression of Wnt and enamel knot–related genes, influencing epithelial cell rearrangements and subsequent cusp patterning."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, genetic studies have identified coding variants in APCDD1 in familial colorectal cancer cases, and functional analyses in breast cancer models indicate that APCDD1 can suppress canonical Wnt signaling, pointing to its potential tumor‐suppressive role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the context of developmental neurological disorders, analyses of patient cells have implicated APCDD1 as part of a deregulated network affecting both Wnt signaling and cellular adhesion, linking its function to intellectual disability and autism spectrum disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, gene expression profiling during adipogenic differentiation further supports APCDD1 as a marker of cell state, reinforcing its role as an inhibitor of Wnt activity during lineage commitment"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and its dynamic expression in specific epithelial domains, such as the leading edge of developing eyelids, suggests that APCDD1 contributes to the spatial modulation of Wnt signals during morphogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Additionally, the successful targeting of the Drapc1 gene, the murine homolog of human APCDD1, in conditional knockout models has further validated its role in developmental processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomi Jukkola, Natalia Sinjushina, Juha Partanen "}, {"type": "b", "children": [{"type": "t", "text": "Drapc1 expression during mouse embryonic development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Expr Patterns (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.modgep.2004.03.006"}], "href": "https://doi.org/10.1016/j.modgep.2004.03.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15465500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15465500"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Dana W Y Tsui, Y M Doris Lam, Wing S Lee, et al. 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