{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EPHA7, a member of the Eph receptor tyrosine kinase family, exerts multifaceted roles in both normal development and disease. In the nervous system, EPHA7 is expressed by cortical progenitors where its engagement with ephrin ligands is critical for controlling cell number: loss of EPHA7 function reduces apoptosis in neural progenitor cells, thereby increasing cortical size (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", and through its induction of ephrin-A2 reverse signaling, it negatively regulates progenitor proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, EPHA7 is differentially expressed in the developing neocortex, displaying a distinct anteroposterior pattern that is important for the proper topographic formation of corticothalamic projections"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and is a target of post‐transcriptional regulation in the brain (for example, by miR-758;."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, EPHA7 functions predominantly as a tumor suppressor. In follicular lymphoma, for instance, EPHA7 is frequently inactivated by 6q deletions, and a soluble splice variant (EPHA7(TR)) can antagonize pathogenic Eph receptor signaling, thereby blocking oncogenic signals and reducing tumor growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, in colorectal and prostate cancers, promoter hypermethylation leads to downregulation of EPHA7 expression, implicating its loss in tumor progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while expression patterns in breast cancers suggest that EPHA7 may serve as a prognostic marker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, during limb development, EPHA7 is a downstream target of HOXD13; mutations in HOXD13 that impair its ability to transactivate the EPHA7 promoter are associated with complex digital malformations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, EPHA7 is also expressed in dendritic cells derived from CD34+ progenitors, suggesting a potential role in the regulation of immune cell adhesion and trafficking."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these studies reveal that EPHA7 functions as a context‐dependent receptor: it is crucial for fine‐tuning neural development and corticothalamic connectivity, for restraining tumorigenesis in several malignancies via tumor suppressor activities, for mediating aspects of limb morphogenesis downstream of HOXD13, and possibly for modulating immune cell interactions. These diverse roles underscore the potential of EPHA7 both as a biomarker and as a therapeutic target in multiple diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vanessa Depaepe, Nathalie Suarez-Gonzalez, Audrey Dufour, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ephrin signalling controls brain size by regulating apoptosis of neural progenitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature03651"}], "href": "https://doi.org/10.1038/nature03651"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15902206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15902206"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Johan Holmberg, Annika Armulik, Kirsten-André Senti, et al. 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