01868nas a2200337 4500000000100000008004100001260001500042100002200057700001900079700002100098700001600119700001800135700002100153700001700174700001700191700001800208700002500226700002400251700002400275700001800299700001100317700001900328700003000347700002400377700001900401245009500420856005600515300001300571490000800584520093800592 2026 d c2026-09-031 aClaudia V. Nguyen1 aAntoni Martija1 aDaniel C. Jaklic1 aRista White1 aMarty G. Yang1 aPatricia R. Nano1 aJose A. Soto1 aJessenya Mil1 aDakshesh Rana1 aJacqueline M. Martin1 aHunter E. Schweiger1 aSebastian Hernandez1 aElisa Fazzari1 aYu Liu1 aJack M. Parent1 aMohammed A. Mostajo-Radji1 aDaniel H. Geschwind1 aAparna Bhaduri00aThalamic NRXN1-mediated input to human cortical progenitors drives excitatory neurogenesis uhttps://www.science.org/doi/10.1126/science.ady5180 aeady51800 v3933 aThe human cerebral cortex develops through coordinated signals from within the cortex and from other brain regions, including the thalamus. However, how thalamic neuronal projections influence early human cortical development remains less well-understood. In this study, we fused cortical and thalamic organoids to investigate how thalamic input shapes the maturation of human cortical cells. Using single-nuclei RNA-sequencing and cellular imaging, we found that thalamic input increases the production of cortical excitatory neurons. We identify neurexin-1 (NRXN1) as a mediator of physical contact between thalamic axons and cortical outer radial glia. Genetic knockout of thalamic NRXN1 reduced these contacts and attenuated the production of upper-layer excitatory neurons. These findings reveal a mechanism by which thalamic input regulates human cortical progenitors and shapes excitatory neuron production during development.