AbstractCurrently little is known about neuronal positioning and the roles of neuronal primary cilia in postnatal neurodevelopment. Here we show that primary cilia of principal neurons do not fully arise until the postnatal stage, and they undergo marked changes in positioning and orientation, concurrent with postnatal principal neuron positioning and maturation in the mouse cerebral cortex. Primary cilia of early – and late-born CA1 principal neurons display opposite orientations, while primary cilia of principal neurons in the subiculum, entorhinal cortex, and neocortex largely point in the direction of the pia. In contrast, astrocytes and interneurons in the hippocampus, and neurons in nucleated brain regions do not display specific cilia directionality. Guided by the clue of cilia directionality, we discovered that the cell bodies of principal neurons in the hippocampal CA1 superficial sublayer, subiculum, postsubiculum, and neocortex undergo a previously unnoticed, slow but substantial “reverse movement” for postnatal positioning and lamina refinement. Further, selective disruption of cilia function in the forebrain using Ift88 conditional knockout mice leads to cortical expansion, altered cortical lamination, or gyrification in the retrosplenial cortex that is formed through a reverse movement. Collectively, this work has identified reverse movement as a fundamental process for principal cell positioning that refines lamination in the cerebral cortex and may impact the cortical evolution of mammals.
