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Here, single\u2010nucleus RNA sequencing of the superior temporal plane from mid\u2010gestation NSCLP fetuses is performed, and profound alterations in cell\u2010type composition, intercellular communication, and transcriptional programs are uncovered. Integrative analyses with weighted gene co\u2010expression network analysis\u00a0and single\u2010cell regulatory network interference and clustering based on single\u2010nucleus transcriptomes identify myocyte enhancer factor 2C (MEF2C) as a shared transcriptional regulator consistently downregulated in excitatory and inhibitory neurons across mid\u2010term gestation, which is validated in NSCLP fetal brain tissues. MEF2C expression is negatively correlated with synaptophysin\u00a0immunofluorescence intensity. In MEF2C\u2010deficient primary cortical neurons, impaired synaptic formation, reduced postsynaptic density protein\u201095\u00a0expression, and weakened excitatory postsynaptic transmission without altering intrinsic excitability are found. Upstream regulators of MEF2C are enriched for pathways controlling neuronal differentiation, synaptic plasticity, and epigenetic regulation, suggesting broad disruption of neurodevelopmental programs. Together, this study provides molecular evidence of disrupted brain development in NSCLP and implicates MEF2C as a potential mediator of neurodevelopmental impairments.<\/jats:p>","DOI":"10.1002\/advs.202504191","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T18:15:09Z","timestamp":1761070509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Nucleus RNA Sequencing Reveals Mid\u2010Gestational Neurodevelopment Features in the Superior Temporal Plane from Fetuses with Nonsyndromic Cleft Lip and Palate"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-5969","authenticated-orcid":false,"given":"Liu\u2010Lin","family":"Xiong","sequence":"first","affiliation":[{"name":"Institute of Neuroscience Kunming Medical University  Kunming 650500 China"},{"name":"Department of Anesthesiology The Third Affiliated Hospital of Zunyi Medical 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