Endocannabinoid Functions in Neurogenesis, Neuronal Migration, and Specification

Endocannabinoids act as retrograde messengers thus controlling many synapses in the postnatal brain. In contrast, the concept that endocannabinoid functions are pivotal to fundamental developmental processes, including progeni- tor proliferation and fate specification, lineage segregation, neuronal migration, differentiation and survival, in the embryonic brain has just begun to emerge. Understanding the basic developmental and signaling principles controlled by endocannabinoids is pertinent to defining the molecular mechanisms establishing functional neuronal circuits with particular emphasis on synapse specification and functional diversification. Deciphering the spatial and temporal context of endocannabinoid signaling will also reveal the molecular substrates of permanent modifications to cellular structure and functions imposed by in utero cannabis exposure. Here, we review the ontogeny and recently identified functions of the endocannabi- noid system with emphasis on the neuronal lineage during brain development, and discuss how fetal cannabis exposure may modify neuronal networks such that long- term changes to cognitive functions manifest in the affected offspring.