{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts mention SNORD45A, they collectively illustrate the multifaceted functions of the homeobox transcription factor Prox1. Prox1 acts as a master regulator during vascular and lymphatic development by initiating a cell‐fate switch in a subset of venous endothelial cells. Its expression is both necessary and sufficient to trigger the budding and differentiation of lymphatic endothelial cells (LECs) from the cardinal vein, to maintain their identity via positive feedback loops (e.g., via VEGFR3), and to regulate valve formation and lymphovenous communication. These studies also show that Prox1 dosage is critical; subtle alterations in its levels can result in profound developmental defects, with implications for adult-onset obesity, lymphatic dysfunction, and other vascular diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the developing nervous system, Prox1 plays an equally pivotal role in controlling both the timing of cell-cycle exit and the commitment to distinct neuronal lineages. Experimental evidence demonstrates that Prox1 promotes differentiation in retinal progenitors, specifies horizontal cell fate in the retina, and is essential for the maturation of dentate granule neurons in the hippocampus. In addition, its temporally regulated expression is critical for the proper formation of inner ear sensory epithelia and for establishing the identity of specific cortical interneuron subtypes. Collectively, these findings underscore Prox1’s importance in neural and sensory development as a determinant of when and how progenitor cells adopt mature phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in vascular and neural development, Prox1 is indispensably involved in regulating differentiation and morphogenesis in multiple organ systems. It guides hepatocyte and pancreatic precursor migration and specification, modulates transcriptional programs critical for establishing myocardial and skeletal muscle fiber identities, and even influences metabolic homeostasis through interactions with nuclear receptor networks. Moreover, alterations in Prox1 function have been linked to oncogenic processes such as those observed in vascular neoplasms and hepatocellular carcinoma, where its dysregulation contributes to aberrant angiogenesis and tumor progression. In essence, Prox1 emerges as a versatile transcriptional switch that integrates intrinsic developmental cues with extrinsic signals to govern cell fate decisions across diverse tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jeffrey T Wigle, Natasha Harvey, Michael Detmar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/21.7.1505"}], "href": "https://doi.org/10.1093/emboj/21.7.1505"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11927535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11927535"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Natasha L Harvey, R Sathish Srinivasan, Miriam E Dillard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1642"}], "href": "https://doi.org/10.1038/ng1642"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16170315"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16170315"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nicole C Johnson, Miriam E Dillard, Peter Baluk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1727208"}], "href": "https://doi.org/10.1101/gad.1727208"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19056883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19056883"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michael J Flister, Andrew Wilber, Kelly L Hall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-12-196840"}], "href": "https://doi.org/10.1182/blood-2008-12-196840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19901262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19901262"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "R Sathish Srinivasan, Xin Geng, Ying Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nuclear hormone receptor Coup-TFII is required for the initiation and early maintenance of Prox1 expression in lymphatic endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.1859310"}], "href": "https://doi.org/10.1101/gad.1859310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20360386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20360386"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ying Yang, José Manuel García-Verdugo, Mario Soriano-Navarro, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Embryonic vascular endothelial cells are malleable to reprogramming via Prox1 to a lymphatic gene signature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Dev Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-213X-10-72"}], "href": "https://doi.org/10.1186/1471-213X-10-72"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20584329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20584329"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Maximilianos Elkouris, Nikos Balaskas, Maria Poulou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/stem.554"}], "href": "https://doi.org/10.1002/stem.554"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21280160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21280160"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Riikka Kivelä, Ida Salmela, Yen Hoang Nguyen, et al. 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