Developmental Transcriptomic Trajectories Define Forebrain-Projecting Serotonin System Organization

We found that serotonin neuron heterogeneity was established embryonically and that the subtype taxonomy was largely conserved between mice and humans. Across serotonin subtypes, we observed a coordinated surge in wiring molecule expression at mouse postnatal day 4 that aligned with the subsequent global innervation wave.

Tracing subtypes defined by developmentally conserved markers at birth revealed complementary projection territories and engagement of distinct postnatal wiring modules that matched region specific terminal maturation. Together, these results show that brain wide serotonin innervation is built through embryonic subtype specification and two layers of postnatal control: system level synchronization and subtype specific terminal development.