Deep-layer neurons compensate for the loss of layer 4 sensory recipient cells in the developing neocortex

Layer 4 cortical neurons are key sensory recipients of thalamocortical inputs, facilitating higher-order information processing. Layer 4 cell fate is determined by intrinsic transcriptional programs and extrinsic cues, yet the extent to which layer 4 cell identity is fixed remains unclear. Here, we investigate cortical fate plasticity using a tamoxifen-inducible conditional ablation to selectively eliminate layer 4-destined neurons at their earliest postmitotic stage. We found that, despite the depletion of these cells, the overall layer 4 neuron population remains intact, suggesting a compensatory mechanism. Birthdate labeling and molecular analysis revealed that earlier-born deep-layer neurons, rather than later-born upper-layer neurons, adopt a layer 4 identity in response to this loss. This fate shift is associated with altered Foxg1 downregulation and Nr2f1 upregulation, suggesting a molecular switch governing adaptive neurogenesis. Collectively, these findings provide new insights into the temporal and spatial constraints of cortical fate determination and reveal a compensatory mechanism that preserves cortical circuit formation despite early neuronal loss.