{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LIX1 (Limb Expression 1) was originally identified as a gene transiently expressed during early limb development and in discrete regions of the embryonic central nervous system (including spinal motor neurons)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Recent studies in gastrointestinal stromal tumours have revealed that LIX1 is strongly up-regulated in these neoplasms, where it regulates proliferation and differentiation of mesenchymal progenitors by modulating the activity of the Hippo pathway effectors YAP1/TAZ; inactivation of LIX1 in this context leads to reduced YAP1/TAZ signalling, down-regulation of KIT, and a shift toward smooth muscle lineage features."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In parallel, investigations into spinal muscular atrophy (SMA) have highlighted LIX1 as a candidate gene due to its predominant expression in spinal motor neurons. In feline SMA, a ~140‐kb deletion removing LIX1 (along with LNPEP) has been implicated in the disease phenotype, suggesting a role in motor neuron maintenance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " However, further studies in human SMA patients and gene trap knockout mice did not reveal clear pathogenic mutations or neuromuscular deficits attributable solely to LIX1 loss, implying possible compensatory mechanisms or species‐specific differences"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings suggest that LIX1 functions as a molecular modulator of cell fate decisions—integrating developmental signals in mesenchymal and neural lineages—and that its dysregulation may impact both oncogenic proliferation in digestive mesenchyme‐derived tumours and motor neuron integrity. Nevertheless, the precise molecular mechanisms underlying LIX1’s roles remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "E C Swindell, C Moeller, C Thaller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cloning and expression analysis of chicken Lix1, a founding member of a novel gene family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mech Dev (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0925-4773(01)00535-4"}], "href": "https://doi.org/10.1016/s0925-4773(01"}, {"type": "t", "text": "00535-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11731258"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11731258"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Amandine Guérin, Delphine Martire, Eva Trenquier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LIX1 regulates YAP activity and controls gastrointestinal cancer cell plasticity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.15569"}], "href": "https://doi.org/10.1111/jcmm.15569"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32633461"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32633461"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "John C Fyfe, Marilyn Menotti-Raymond, Victor A David, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An approximately 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genome Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gr.5268806"}], "href": "https://doi.org/10.1101/gr.5268806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16899656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16899656"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "N J Parkinson, D Baumer, A Rose-Morris, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Candidate screening of the bovine and feline spinal muscular atrophy genes reveals no evidence for involvement in human motor neuron disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuromuscul Disord (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nmd.2008.03.003"}], "href": "https://doi.org/10.1016/j.nmd.2008.03.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18395445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18395445"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Teguh Haryo Sasongko, Gunadi, Surini Yusoff, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Screening of the LIX1 gene in Japanese and Malaysian patients with SMA and/or SMA-like disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.braindev.2009.06.008"}], "href": "https://doi.org/10.1016/j.braindev.2009.06.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19664890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19664890"}]}]}]}