Figure 4.

Identification of a longer fusion isoform of ARHGAP11B expressed in dividing radial glia. (A) Partial duplication (duplicated sequence represented by blue shading) of ARHGAP11A resulted in ARHGAP11B. (B) We identified three isoforms of ARHGAP11B based on full-length transcript sequencing, and these are shown in the context of SDs. The “long” isoform (ARHGAP11B_3) extends deeply into adjacent duplications; a “medium” isoform (ARHGAP11B_5) has four additional exons beyond the duplication shared with ARHGAP11A; and a “short” isoform (AHRGAP11B_6) consists entirely of sequence shared with ARHGAP11A. Note that all three isoforms share the same ORF, and fused exons are predicted to be noncoding. (C) Expression estimates based on short-read RNA-seq data for the three isoforms in select tissues support the prominence of the long isoform but limited evidence for expression of the short isoform. (D) In situ hybridization performed on sections of developing cortical brain (gestational week 18) indicates expression in cells along the ventricle of the ventricular zone (VZ; arrowheads, magnified inset), where radial glia undergo mitosis, consistent with long form of ARHGAP11B expressed specific to dividing ventricular radial glia but missing from outer radial glia. Probe targets are shown in panel A. Probe B is not predicted to hybridize to the ancestral OTUD7A gene (Methods).