Neuronal primary cilia regulate pyramidal cell positioning to the deep and superficial sublayers in the hippocampal CA1

Abstract

AbstractIt is well-recognized that primary cilia regulate embryonic neurodevelopment, but little is known about their roles in postnatal neurodevelopment. The striatum pyramidal (SP) of hippocampal CA1 consists of superficial and deep sublayers, however, it is not well understood how early- and late-born pyramidal neurons position to two sublayers postnatally. Here we show that the axonemes of primary cilia of early-born pyramidal neurons point to the stratum oriens (SO), whereas late-born neuronal cilia orient toward the stratum radiatum (SR), reflecting an inside-out lamination pattern. Neuronal primary cilia in SP undergo marked changes in morphology and orientation from postnatal day 5 (P5) to P14, concurrent with pyramidal cell positioning to the deep and superficial sublayers and with neuronal maturation. Transgenic overexpression of Arl13B, a protein regulating ciliogenesis, not only elongates primary cilia and promotes earlier cilia protrusion, but also affects centriole positioning and cilia orientation in SP. The centrioles of late-born neurons migrate excessively to cluster at SP bottom before primary cilia protrusion and a reverse movement back to the main SP. Similarly, this backward movement of centriole/cilia is also manifested on late-born cortical pyramidal neurons, although early- and late-born cortical neurons display the same cilia orientation. Together, this study provides the first evidence demonstrating that late-born pyramidal neurons exhibit a reverse movement for cell positioning, and primary cilia regulate pyramidal neuronal positioning to the deep and superficial sublayers in the hippocampus.Significance Statement1.Because the axonemes of primary cilia of early-born neurons point to the stratum oriens (SO), whereas late-born neuronal cilia orient toward the opposite direction, neuronal primary cilia orientation can be used as a marker to distinguish early- and late-born pyramidal neurons in the CA1.2.This work is the first to show that neuronal primary cilia modulate pyramidal neuronal positioning to the deep and superficial sublayers of the hippocampal CA1.3.Transgenic overexpression of Arl13B not only elongates primary cilia and promotes earlier cilia protrusion, but also affects centriole positioning and cilia orientation in the CA1.4.We have identified a novel “reverse movement” of late-born CA1 and cortical pyramidal neurons for cell positioning, which may affect the maturation and formation of synaptic connectivity of late-born neurons.