Region Specific Brain Organoids to Study Neurodevelopmental Disorders

Abstract

Region specific brain organoids are brain organoids derived by patterning protocols using extrinsic signals as opposed to cerebral organoids obtained by self-patterning. The main focus of this review is to discuss various region-specific brain organoids developed so far and their application in modeling neurodevelopmental disease. We first discuss the principles of neural axis formation by series of growth factors, such as SHH, WNT, BMP signalings, that are critical to generate various region-specific brain organoids. Then we discuss various neurodevelopmental disorders modeled so far with these region-specific brain organoids, and findings made on mechanism and treatment options for neurodevelopmental disorders (NDD).

Keywords: Brain organoids; Disease modeling; Human pluripotent stem cells; Neurodevelopmental disorders; Region-specific brain organoids.

Fig. 1

Approaches for organoid ge-neration. Unguided approach: Orga-noids are developed based on self-organization principles of stem-cell aggregates resulting in cerebral orga-noids. Cerebral organoids contain heterogeneous population of tissues resembling various embryonic brain vesicles (middle panel). Guided approach: Stem-cell aggregates can be directed to distinct cell fates resulting in region-specific brain organoids in the presence of external patterning cues.