{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPlexin receptors are best recognized for their roles in cell adhesion, migration, and the guidance of developing axons. In the nervous system, Plexin C1 (PLXNC1) serves as a key mediator of semaphorin‐induced signals that shape neuronal migration and synapse formation. For example, in the hypothalamus, proper PLXNC1 expression is required for the normal positioning of vasopressin and oxytocin neurons, and its altered regulation is associated with neuronal mis‐placement ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]. In the olfactory pathway, activity‐dependent cues—most notably Sema7A—engage PLXNC1 expressed on mitral/tufted cell dendrites during a neonatal critical period, promoting post‐synaptic assembly and dendrite selection that influence odor imprinting and connectivity ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "]. Furthermore, studies comparing plexin subfamilies have shown that, similar to Plexin‐D1 and Plexin‐C1, this receptor can modulate R‐Ras activity—a mechanism likely contributing to repulsive guidance signals in developing neurons ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside the nervous system, PLXNC1 has emerged as an important regulator of immune cell behavior and inflammatory responses. In models of acute inflammation, PLXNC1 is expressed by leukocytes where it affects the rolling, adhesion, and transendothelial migration necessary for an effective inflammatory response; indeed, both antibody‐mediated blockade and genetic deletion of PLXNC1 markedly reduce these responses in peritonitis ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]. In the context of pulmonary fibrosis, deficiency of PLXNC1 leads to excessive macrophage migration mediated by synaptotagmin 7 (Syt7), which in turn exacerbates collagen accumulation and fibrotic changes in the lung, an effect reversible by restoring PLXNC1 expression in hematopoietic cells ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]. Recent findings further suggest that PLXNC1 influences intracellular lipopolysaccharide (LPS) sensing and downstream caspase‐11 activation, linking axon guidance molecules to innate immune mechanisms ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPLXNC1 also plays nuanced roles in regulating cell migration and growth in non‐neuronal tissues, with implications for both normal physiology and disease. In melanocytes and primary melanoma cells, PLXNC1 functions as a tumor suppressor by lowering R‐Ras activity, thereby reducing migratory and proliferative capacities; loss of PLXNC1 in melanocytes is associated with increased cell migration that may predispose to early melanoma progression ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "]. Moreover, in the formation of dopaminergic circuits, PLXNC1 expression is tightly coordinated by transcription factors (such as Otx2 and Lmx1a/b) to ensure proper segregation of nigrostriatal and mesolimbic pathways, emphasizing its role in the fine‐tuning of neuronal connectivity and behavior ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]. In a related yet distinct vein, studies of RasL11a—a chromatin‐associated modulator of ribosomal RNA synthesis—highlight broader intracellular signaling networks that intersect with those regulated by plexin receptors, offering insights into how diverse intracellular cues might integrate with PLXNC1‐mediated processes ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "].\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Cheng Xu, Chen-Ming Fan "}, {"type": "b", "children": [{"type": "t", "text": "Allocation of paraventricular and supraoptic neurons requires Sim1 function: a role for a Sim1 downstream gene PlexinC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2007-0034"}], "href": "https://doi.org/10.1210/me.2007-0034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17356169"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17356169"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Nobuko Inoue, Hirofumi Nishizumi, Hiromi Naritsuka, et al. 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