Figure 2.

Strong UBE3A Signal in Neuronal Nuclei in hCOs Correlates to Early Stages of Prenatal Neurodevelopment

(A) Schematics illustrating the simplified cellular and laminar organization of the developing human fetal cortex and that of a typical hCO.

(B) Summary of dynamic UBE3A localization in neurotypical hCOs.

(C) Dotted white lines delineate boundaries between TBR1⁺ and EOMES⁺ regions. Strong nuclear UBE3A in TBR1⁺ cells (arrows), weak nuclear UBE3A in EOMES⁺ cells (arrowheads), and weak UBE3A in cytoplasm of TBR1⁺ cells (double arrows) are seen.

(D) Strong nuclear UBE3A colocalizes with CTIP2⁺/TBR1⁺ cells (arrows).

(E) Strong nuclear UBE3A in TBR1⁺/SATB2⁻ (arrowheads) and TBR1⁺/SATB2⁺ (double arrows) cells and weaker UBE3A in TBR1⁻/SATB2⁺ cells (arrows).

(F) UBE3A localization by cortical cell type identified by immunostaining. Error bars, 95% confidence intervals. n = 3 independent experiments with two organoids in each.

(G) Strong nuclear UBE3A in TBR1⁺/Calretinin⁺ (arrows), TBR1⁺/Calretinin weak (double arrows), and TBR⁺/Calretinin⁻ (arrowheads) neurons.

(See also Figure S3.)