Yen-Chung Chen (New York University)
Minimal Memory, Flexible Fates: Spatial Patterning in the Drosophila Medulla

Spatial patterning subdivides neural progenitors into domains that generate distinct neuron types, but spatial transcription factors are often transient. In most systems, downstream effectors bridge this gap by relaying spatial information to postmitotic cells. In the Drosophila medulla, a visual processing center containing approximately one hundred neuron types, spatial factors disappear as neuroepithelium converts to neural stem cells, and no relay has been identified. Using single-cell multiome profiling, we found that progenitors from different spatial domains converge to near-identical molecular states, except for two spatial factor loci where domain-specific chromatin accessibility persists. These factors are reactivated in postmitotic neurons, where they are sufficient to specify domain-specific fates, and PRC2-mediated repression restricts this reactivation to appropriate domain progeny. Certain neuron types escape spatial patterning entirely through Notch signaling and temporal cues that override spatial factor expression, and these neurons occupy circuit positions where numerical reduction impairs visual processing. Together, our results reveal a minimal chromatin architecture that defers spatial fate execution to neurons, enabling both reliable specification and deterministic exceptions.

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