Developmental emergence of first- and higher-order thalamic neuron molecular identities

The thalamus is organized into nuclei that have distinct input and output connectivities with the cortex. While first-order (FO) nuclei - also called core nuclei - relay input from sensory organs on the body surface and project to primary cortical sensory areas, higher-order (HO) nuclei - matrix nuclei - instead receive their driver input from the cortex and project to secondary and associative areas within cortico-thalamo-cortical loops. Input-dependent processes have been shown to play a critical role in the emergence of FO thalamic neuron identity from a ground state HO neuron identity, yet how this identity emerges during development remains unknown. Here, using single-cell RNA sequencing of the developing embryonic thalamus, we show that FO thalamic identity emerges after HO identity and that peripheral input is critical for the maturation of excitatory, but not inhibitory FO-type neurons. Our findings reveal that subsets of HO neurons are developmentally co-opted into FO-type neurons, providing a mechanistic framework for the diversification of thalamic neuron types during development and evolution. Summary StatementSubsets of higher-order thalamic neurons are developmentally co-opted into first-order type neurons, providing a framework for the diversification of thalamic neuron types during development and evolution.