Mapping of neuronal and glial primary cilia contactome and connectome in the human cerebral cortex.

Primary cilia act as antenna receivers of environmental signals and enable effective neuronal or glial responses. Disruption of their function is associated with circuit disorders. To understand the signals these cilia receive, we comprehensively mapped cilia's contacts within the human cortical connectome using serial-section EM reconstruction of a 1 mm3 cortical volume, spanning the entire cortical thickness. We mapped the "contactome" of cilia emerging from neurons and astrocytes in every cortical layer. Depending on the layer and cell type, cilia make distinct patterns of contact. Primary cilia display cell-type- and layer-specific variations in size, shape, and microtubule axoneme core, which may affect their signaling competencies. Neuronal cilia are intrinsic components of a subset of cortical synapses and thus a part of the connectome. This diversity in the structure, contactome, and connectome of primary cilia endows each neuron or glial cell with a unique barcode of access to the surrounding neural circuitry.

Coordinating cerebral cortical construction and connectivity: Unifying influence of radial progenitors.

Radial progenitor development and function lay the foundation for the construction of the cerebral cortex. Radial glial scaffold, through its functions as a source of neurogenic progenitors and neuronal migration guide, is thought to provide a template for the formation of the cerebral cortex. Emerging evidence is challenging this limited view. Intriguingly, radial glial scaffold may also play a role in axonal growth, guidance, and neuronal connectivity. Radial glial cells not only facilitate the generation, placement, and allocation of neurons in the cortex but also regulate how they wire up. The organization and function of radial glial cells may thus be a unifying feature of the developing cortex that helps to precisely coordinate the right patterns of neurogenesis, neuronal placement, and connectivity necessary for the emergence of a functional cerebral cortex. This perspective critically explores this emerging view and its impact in the context of human brain development and disorders.