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Recently, we reported that <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3 is expressed in mouse cerebral cortex throughout the developmental process, especially at early embryonic stage. We thus examined the role of <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3 in the development of the mouse cerebral cortex. Acute silencing of <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3 with <jats:italic>in utero<\/jats:italic> electroporation method caused positional defects of excitatory neurons during corticogenesis. Time\u2010lapse imaging revealed that the abnormal positioning was at least partially because of the reduced migration velocity. When <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3 was silenced in cortical neurons in one hemisphere, axon extension to the contralateral hemisphere was also delayed. These aberrant phenotypes were rescued by <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>i\u2010resistant <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3. Notably, knockdown of <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3 did not affect the cell cycle of neuronal progenitors and stem cells at the ventricular zone. Taken together, <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3 was thought to play a crucial role in corticogenesis through the regulation of excitatory neuron migration and axon extension. Meanwhile, when we performed comparative genomic hybridization on a patient with specific learning disorders, a 107 Kb\u2010deletion was identified on 18q12.3 (nt. 39554147\u201339661206) that encompasses exons 5\u201323 of <jats:italic><jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3<\/jats:italic>. Notably, the above aberrant migration and axon growth phenotypes were not rescued by the disease\u2010related truncation mutant (172 amino acids) lacking the C\u2010terminal kinase domain. Thus, functional defects of <jats:styled-content style=\"fixed-case\">PIK<\/jats:styled-content>3C3 might impair corticogenesis and relate to the pathophysiology of specific learning disorders and other neurodevelopmental disorders.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13832-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nAcute knockdown of Class III phosphoinositide 3\u2010kinase (PIK3C3) evokes migration defects of excitatory neurons during corticogenesis. PIK3C3\u2010knockdown also disrupts axon outgrowth, but not progenitor proliferation <jats:italic>in\u00a0vivo<\/jats:italic>. Involvement of PIK3C3 in neurodevelopmental disorders might be an interesting future subject since a deletion mutation in <jats:italic>PIK3C3<\/jats:italic> was detected in a patient with specific learning disorders (SLD).\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13832","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T18:47:49Z","timestamp":1473360469000},"page":"245-255","source":"Crossref","is-referenced-by-count":14,"title":["Role of Class III phosphoinositide 3\u2010kinase in the brain development: possible involvement in specific learning disorders"],"prefix":"10.1111","volume":"139","author":[{"given":"Yutaka","family":"Inaguma","sequence":"first","affiliation":[{"name":"Department of Molecular Neurobiology Institute for Developmental Research Aichi Human Service Center Kasugai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of 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