GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE310nnn/GSE310138/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310138GEOGSEfalseSex-Biased Transcription in Early Postnatal Layer 2/3 Cortical Neurons: Interplay Between Sex and Cux1/2 MutationsDespite many neurodevelopmental disorders (NDDs) exhibiting pronounced sex differences, the role of sex in shaping the genetic regulation of the brain remains barely explored. Brain development relies on a precise control of gene expression across time and disruptions in this process, especially during critical periods, can result in NDDs. In the neocortex, layer (L) 2/3 excitatory pyramidal neurons stand out for integrating information across cortical areas and hemispheres. Here, we show a transient window of sex-biased gene expression of L2/3 neurons at postnatal day 4 (P4), mainly characterized by autosomal genes. Loss-of-function experiments targeting Cux1 and Cux2, key transcription factors in L2/3 development, lead to sex-dependent transcriptional deregulation in these neurons, with a significant male-biased sensitivity. Moreover, differentially expressed genes shift substantially between developmental stages, reflecting the dynamic regulation of Cux-mediated gene expression. Overall, our study identifies P4 as a key determinant of early sex differences and highly vulnerable stage for the emergence of NDDs, and highlights the importance of sex-specific analyses for understanding brain development and disease.2026/05/20GSE310138GSM9289418GSM9289419GSM9289405GSM9289406GSM9289403GSM9289404GSM9289401GSM9289402GSM9289388GSM9289389GSM9289400GSM9289386GSM9289387GSM9289384GSM9289385GSM9289382GSM9289383GSM9289380GSM9289381GSM9289390GSM9289409GSM9289407GSM9289408GSM9289416GSM9289417GSM9289414GSM9289415GSM9289412GSM9289379GSM9289413GSM9289399GSM9289410GSM9289377GSM9289378GSM9289411GSM9289397GSM9289398GSM9289395GSM9289396GSM9289393GSM9289394GSM9289391GSM928939230172310138Mus musculus[41952201]