TY - JOUR
AU - Claudia V. Nguyen
AU - Antoni Martija
AU - Daniel C. Jaklic
AU - Rista White
AU - Marty G. Yang
AU - Patricia R. Nano
AU - Jose A. Soto
AU - Jessenya Mil
AU - Dakshesh Rana
AU - Jacqueline M. Martin
AU - Hunter E. Schweiger
AU - Sebastian Hernandez
AU - Elisa Fazzari
AU - Yu Liu
AU - Jack M. Parent
AU - Mohammed A. Mostajo-Radji
AU - Daniel H. Geschwind
AU - Aparna Bhaduri
AB - The 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.
BT - Science
DA - 2026-09-03
DO - 10.1126/science.ady5180
IS - 6815
N2 - The 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.
PY - 2026
EP - eady5180
T2 - Science
TI - Thalamic NRXN1-mediated input to human cortical progenitors drives excitatory neurogenesis
UR - https://www.science.org/doi/10.1126/science.ady5180
VL - 393
Y2 - 2026-09-04
ER -