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Chunk #10 — Global transcriptome dynamics — Spatiotemporal differential exon usage

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Spatio-temporal transcriptome of the human brain.
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Focusing on ANKRD32, a gene we have previously shown to express an alternative variant in the late midfetal frontal cortex17, we confirmed and extended DEU findings by revealing that while the longer isoform (ANKRD32a) was equally expressed across fetal NCX areas, the shorter isoform (ANKRD32b), comprising the last three exons, exhibited dynamic areal patterns. ANKRD32b was transiently expressed in a gradient along the anterior-posterior axis of the midfetal frontal cortex, with the highest expression in OFC and lowest in M1C. Prior to this, ANKRD32b was most highly enriched in the ITC and, to a lesser extent, in the STC. These spatiotemporal patterns disappeared after birth, when only ANKRD32a was expressed, and were not observed in the mouse NCX of equivalent periods (Supplementary Fig. 16; Supplementary Table 6). These findings illustrate the complexity of DEU in the human brain and demonstrate how specific alternative transcripts can be spatially restricted during a narrow developmental window and with inter-species differences.