Deciphering and reconstitution of positional information in the human brain development

Organoid has become a novel in vitro model to research human development and relevant disorders in recent years.With many improvements on the culture protocols, current brain organoids could self-organize into a complicatedthree-dimensional organization that mimics most of the features of the real human brain at the molecular, cellular,and further physiological level. However, lacking positional information, an important characteristic conveyedby gradients of signaling molecules called morphogens, leads to the deficiency of spatiotemporally regulated cellarrangements and cell–cell interactions in the brain organoid development. In this review, we will overview the roleof morphogen both in the vertebrate neural development in vivo as well as the brain organoid culture in vitro, thestrategies to apply morphogen concentration gradients in the organoid system and future perspectives of the brainorganoid technology.