Long non-coding RNA LncKdm2b regulates cortical neuronal differentiation by cis-activating Kdm2b

Abstract

The mammalian cerebral cortex, also known as the neocortex, is a six-layered structure and responsible for performing the most sophisticated cognitive and perceptual functions such as sensory perception, generation of motor commands, conscious thought and language. The adult neocortex comprises a plethora of projection neurons, interneurons and glial cells. Projection neurons (PNs) are the main functional units, expressing excitatory neurotransmitters, with their long axons projecting into subcortical regions or contralateral cortex of the brain. In mice, cortical PNs are largely generated between embryonic (E) day 11.5 to E17.5 indirectly from radial glial progenitor cells (RGPCs), whose nuclei lie in the region close to the lateral ventricles, ventricular zone (VZ). RGPCs usually divide asymmetrically to self-renew and simultaneously give rise to intermediate progenitor cells (IPCs), which are multipolar and reside basally to RGPCs in the subventricular zone (SVZ). IPCs divide symmetrically to generate either two IPCs or two postmitotic PNs. PNs then migrate radially along the basal processes of RGPCs to propagate the cortical plate (CP) in the basal part of the cortex, which eventually forms cortical layers (Fietz and Huttner, 2011 ; Kwan et al., 2012 ). Many cellular and molecular aspects governing cortical neurogenesis have been extensively studied, including cell-autonomous and non-autonomous regulation of RGPCs’ asymmetric cell division, neuronal fate commitment, as well as PNs’ radial migration (Ayala et al., 2007 ; Greig et al., 2013 ; Imayoshi and Kageyama, 2014 ). However, mechanisms that control the initial numbers and proliferation rates of RGPCs, as well as the proliferative or neurogenic choices of IPCs, are largely elusive (Greig et al., 2013 ; Homem et al., 2015 ).