{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FRMD7 is a FERM‐domain–containing protein that plays a pivotal role in neuronal development and the establishment of ocular motor circuits. During early embryonic and fetal stages, FRMD7 expression is tightly regulated and is restricted to regions important for eye movement control, including the developing brain, retina, and brainstem."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Functional studies have shown that reduction or mutation of FRMD7 perturbs neurite outgrowth during retinoic acid–induced differentiation, indicating its key involvement in neuronal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, FRMD7 interacts with plasma membrane–associated proteins such as CASK, which recruits FRMD7 to the plasma membrane to promote neurite extension, thereby supporting the development of the oculomotor neural network."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, FRMD7 directly binds to the Rho GTPase regulator RhoGDIα to facilitate the activation of Rac1 signaling; this pathway is crucial for the reorganization of actin filaments and the proper establishment of neuronal morphology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Finally, studies in both humans and animal models indicate that FRMD7 is essential for establishing neuronal circuit asymmetries in the retina. Loss of FRMD7 function leads to impaired horizontal direction selectivity of retinal ganglion cells and abnormalities in the optokinetic reflex, which are thought to underlie the ocular oscillations observed in idiopathic congenital nystagmus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted role of FRMD7 in orchestrating neuronal development and in the formation of ocular motor circuits. Disruption of FRMD7 function, whether by mutation or altered expression, compromises cytoskeletal dynamics and circuit asymmetry, ultimately leading to disorders of gaze stability such as idiopathic congenital nystagmus.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Patrick Tarpey, Shery Thomas, Nagini Sarvananthan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1893"}], "href": "https://doi.org/10.1038/ng1893"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17013395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17013395"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Joanne Betts-Henderson, Stefano Bartesaghi, Moira Crosier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nystagmus-associated FRMD7 gene regulates neuronal outgrowth and development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp500"}], "href": "https://doi.org/10.1093/hmg/ddp500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19892780"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19892780"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Rachel J Watkins, Rajashree Patil, Benjamin T Goult, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel interaction between FRMD7 and CASK: evidence for a causal role in idiopathic infantile nystagmus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt060"}], "href": "https://doi.org/10.1093/hmg/ddt060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23406872"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23406872"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jiali Pu, Yanfang Mao, Xiaoguang Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FERM domain containing protein 7 interacts with the Rho GDP dissociation inhibitor and specifically activates Rac1 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0073108"}], "href": "https://doi.org/10.1371/journal.pone.0073108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23967341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23967341"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Keisuke Yonehara, Michele Fiscella, Antonia Drinnenberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuron (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuron.2015.11.032"}], "href": "https://doi.org/10.1016/j.neuron.2015.11.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26711119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26711119"}]}]}]}