Endocannabinoids via CB1 receptors act as neurogenic niche cues during cortical development

Abstract

During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturation. Thus, the CB1 cannabinoid receptor in concert with locally produced ECBs regulates neural progenitor (NP) proliferation, pyramidal specification and axonal navigation. In addition, subcellularly restricted ECB production acts as an axonal growth cone signal to regulate interneuron morphogenesis. These findings provide the rationale for understanding better the consequences of prenatal cannabinoid exposure, and emphasize a novel role of ECBs as neurogenic instructive cues involved in cortical development. In this review the implications of altered CB1-receptor-mediated signalling in developmental disorders and particularly in epileptogenesis are briefly discussed. © 2012 The Royal Society.