{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fibroblast growth factor 17 (FGF17) is a multifunctional secreted signaling molecule that plays diverse roles during embryonic development and in disease. In the limb, FGF17 is one of several apical ectodermal ridge–derived FGFs; however, its loss (even together with Fgf4 and Fgf9) does not disturb skeletal patterning provided Fgf8 is maintained (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In contrast, in the developing brain FGF17 has critical region‐ and context–specific roles. It is expressed in rostral patterning centers of the telencephalon where it contributes to the specification and growth of dorsal frontal cortical areas; accordingly, loss of Fgf17 leads to selective reduction of dorsal frontal cortex and shifts in the organization of sensory areas (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Consistent with its neurodevelopmental function, Fgf17‐deficient mice display distinct deficits in social behaviors, including decreased neonatal vocalizations and impaired social recognition in adults (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " At the molecular level, receptor–binding analyses demonstrate that the FGF17b isoform exhibits intermediate affinities for fibroblast growth factor receptors compared with related family members (notably FGF8 and FGF18), a property that likely underpins its unique patterning activity in mid–hindbrain and cortical regions (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, mutations in FGF17 have been identified in patients with congenital hypogonadotropic hypogonadism, supporting a role for FGF17 in neuroendocrine as well as reproductive axis development (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, aberrant up–regulation of FGF17 has been observed in certain cancers – for example, in hepatocellular carcinoma and colorectal cancer, where enhanced FGF17 signaling appears to promote cell survival and tumor progression through autocrine and paracrine mechanisms (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, developmental studies indicate that perturbations in upstream regulators (such as Mid1) can down–regulate Fgf17 expression and disrupt proper brain morphogenesis at critical boundaries (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings underscore that FGF17 is a key determinant in embryonic patterning, particularly in brain development and function, with implications for neurodevelopmental disorders and oncogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesca V Mariani, Christina P Ahn, Gail R Martin "}, {"type": "b", "children": [{"type": "t", "text": "Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06876"}], "href": "https://doi.org/10.1038/nature06876"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18449196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18449196"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Y Maruoka, N Ohbayashi, M Hoshikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mech Dev (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0925-4773(98)00061-6"}], "href": "https://doi.org/10.1016/s0925-4773(98"}, {"type": "t", "text": "00061-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9651520"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9651520"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shaun K Olsen, James Y H Li, Carrie Bromleigh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1365406"}], "href": "https://doi.org/10.1101/gad.1365406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16384934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16384934"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jeremy A Cholfin, John L R Rubenstein "}, {"type": "b", "children": [{"type": "t", "text": "Frontal cortex subdivision patterning is coordinately regulated by Fgf8, Fgf17, and Emx2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Comp Neurol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cne.21709"}], "href": "https://doi.org/10.1002/cne.21709"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18459137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18459137"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yongping Wang, Lanying Song, Chengji J Zhou "}, {"type": "b", "children": [{"type": "t", "text": "The canonical Wnt/β-catenin signaling pathway regulates Fgf signaling for early facial development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ydbio.2010.11.004"}], "href": "https://doi.org/10.1016/j.ydbio.2010.11.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21070765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21070765"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Rachel E Thomson, Peter C Kind, Nicholas A Graham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neural Dev (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1749-8104-4-4"}], "href": "https://doi.org/10.1186/1749-8104-4-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19192266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19192266"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "K Scearce-Levie, E D Roberson, H Gerstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal social behaviors in mice lacking Fgf17."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Brain Behav (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1601-183X.2007.00357.x"}], "href": "https://doi.org/10.1111/j.1601-183X.2007.00357.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17908176"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17908176"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hichem Miraoui, Andrew A Dwyer, Gerasimos P Sykiotis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2013.04.008"}], "href": "https://doi.org/10.1016/j.ajhg.2013.04.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23643382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23643382"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Christine Gauglhofer, Sandra Sagmeister, Waltraud Schrottmaier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of the fibroblast growth factor 8 subfamily in human hepatocellular carcinoma for cell survival and neoangiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.24099"}], "href": "https://doi.org/10.1002/hep.24099"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21319186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21319186"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Rui Liu, Shan Huang, Yunlong Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FGF8 promotes colorectal cancer growth and metastasis by activating YAP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2822"}], "href": "https://doi.org/10.18632/oncotarget.2822"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25473897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25473897"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Alessio Lancioni, Mariateresa Pizzo, Bianca Fontanella, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of Mid1, the mouse ortholog of the Opitz syndrome gene, causes abnormal development of the anterior cerebellar vermis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4196-09.2010"}], "href": "https://doi.org/10.1523/JNEUROSCI.4196-09.2010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20181585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20181585"}]}]}]}