Source data - The identity gene Fezf2 is repurposed postnatally to specify inhibitory input in an activity-dependent manner.

Pyramidal cells recruit inhibitory synapses in proportion to their activity, but it is unclear whether pyramidal cell subtypes use distinct mechanisms to acquire cell-type specific levels of inhibition. Here, we show that a neuronal identity gene is repurposed to regulate inhibitory connectivity.

Fezf2, a transcription factor that establishes the identity of extratelencephalic pyramidal cells in layer 5 during embryonic development, is regulated by activity after birth only in those neurons. Activity-dependent Fezf2 controls the number of inhibitory synapses formed by parvalbumin-expressing interneurons through regulation of the cell-surface protein Cadherin-22. Our findings reveal a mechanism for cell-type specificity within activity-dependent circuit development through the redeployment of genes that establish neuronal subtype identity.</p>