Ontogenetic Establishment of Order-specific Nuclear Organization in the Mammalian Thalamus

The thalamus connects the cortex with other brain regions and supports sensory perception, movement, and cognitive functions via numerous distinct nuclei. However, the mechanisms underlying the development and organization of diverse thalamic nuclei remain largely unknown. Here we report an intricate ontogenetic logic of mouse thalamic structures. Individual radial glial progenitors in the developing thalamus actively divide and produce a cohort of neuronal progeny that exhibits striking spatial configuration and nuclear occupation related to functionality. While the anterior clonal cluster displays relatively more tangential dispersion and contributes predominantly to nuclei with cognitive functions, the medial ventral posterior clonal cluster forms prominent radial arrays and contributes mostly to nuclei with sensory/motor-related activities. Moreover, the first-order and higher-order sensory/motor nuclei across different modalities are largely segregated clonally. Notably, the Shh signaling activity influences clonal spatial distribution. Our study reveals lineage relationship to be a critical regulator of non-laminated thalamus development and organization.