{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:32:44Z","timestamp":1790767964593,"version":"4.1.0"},"reference-count":52,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T00:00:00Z","timestamp":1763424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Roy J. Carver Foundation"},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS136448"],"award-info":[{"award-number":["R01 NS136448"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Iowa Graduate College"},{"name":"Iowa Neuroscience Institute"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Huntington's Disease"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:p>\n                    Huntington's disease (HD) is classically characterized as a late-onset neurodegenerative disorder of adulthood caused by CAG expansion in the\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    gene. However, mounting evidence from both human and experimental studies suggests that both wild-type and mutant huntingtin play important roles during brain development. In this review, we examine the developmental functions of huntingtin, including its role in neuronal migration, synaptogenesis, suppression of apoptosis, mitotic spindle orientation, and transcriptional regulation. We also discuss how mutant\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    may act through both loss- and gain-of-function mechanisms during early brain development. Comparative evolutionary analysis suggests that\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    is highly conserved and that the emergence of the N-terminal polyglutamine tract may have conferred developmental advantages in organisms with more complex nervous systems. Interestingly, studies in pre-symptomatic human carriers and mouse models have identified potential early-life cognitive benefits associated with moderate CAG expansion, raising the possibility of antagonistic pleiotropy. Understanding huntingtin's dual function in neurodevelopment and degeneration is essential in gaining insights into the earliest stages of HD pathogenesis, long before clinical onset.\n                  <\/jats:p>","DOI":"10.1177\/18796397251395783","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:22:22Z","timestamp":1763490142000},"page":"226-234","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Huntington's as a developmental disorder: Molecular and neuropathologic considerations"],"prefix":"10.1177","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6696-0720","authenticated-orcid":false,"given":"Mallory R.","family":"Shin","sequence":"first","affiliation":[{"name":"University of Iowa"},{"name":"Interdisciplinary Neuroscience Graduate Program, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3127-4528","authenticated-orcid":false,"given":"Marco M.","family":"Hefti","sequence":"additional","affiliation":[{"name":"University of Iowa"},{"name":"Interdisciplinary Neuroscience Graduate Program, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.02.003"},{"key":"e_1_3_3_3_2","article-title":"Huntington's disease: a clinical review","volume":"14","author":"Andhale R","year":"2022","unstructured":"Andhale R, Shrivastava D. 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