Neuronal polarization in vivo: Growing in a complex environment

•There are the 'inheritance of polarity' mode and the 'establishment of polarity' mode in vivo.•The initial step of neuronal polarization in vivo is axon specification.•Pioneering axons and secreted factors make microenvironment for neuronal polarization in vivo.

Neurons are one of the most polarized cell types in the body. During the past three decades, many researchers have attempted to understand the mechanisms of neuronal polarization using cultured neurons. Although these studies have succeeded in discovering the various signal molecules that regulate neuronal polarization, one major question remains unanswered: how do neurons polarize in vivo?