Biology subjects

Serdar, L.

Publications and source records attributed to Serdar, L..

2 recordsLinked to original sources

bioRxiv2025

Subcellular transcriptome of radial glia reveals compartmentalized control of cortical development

RNA localization and local translation mediate spatial and temporal control of polarized cells, including radial glial cells (RGCs) which produce and organize neurons and glia. Within RGCs, RNAs are transported long distances to basal endfeet, where they can undergo local translation. However, the subcellular composition of RGCs and function of local gene regulation remains largely unknown. Here, we discover that basal endfeet harbor a rich transcriptome including a Dynein component critical for subcellular RGC function. By purifying RGC compartments in vivo, we discover [~]3000 endfoot transcripts, including [~]800 highly enriched compared to cell bodies. Many endfoot-enriched transcripts exhibit conserved subcellular localization in neurons and glia and are associated with neurodevelopmental disease. We show that endfoot-enriched Dync1li2 regulates RGC basal morphology and subsequently interneuron organization. Finally, we develop LOCAL-KD, a CRISPR-Cas13 based method for subcellular mRNA knockdown in vivo. Leveraging this, we demonstrate that endfoot-localized Dync1li2 is critical for RGC morphology. Our study establishes experimental paradigms to understand RNA localization in the nervous system. Moreover, we discover RGCs have a vast subcellular transcriptome, revealing foundational insights into how RGCs control cortical development.

neuroscience↗

bioRxiv2024

mRNA stability fine tunes gene expression in the developing cortex to control neurogenesis

RNA expression levels are controlled by the complementary processes of synthesis and degradation. Although mis-regulation of RNA turnover is linked to neurodevelopmental disorders, how it contributes to cortical development is largely unknown. Here, we profile the RNA stability landscape of the cortex across development and demonstrate that control of stability by the CCR4-NOT complex is essential for corticogenesis in vivo. First, we use SLAM-seq to measure RNA half-lives transcriptome-wide across multiple stages of cortical development. We characterize cis-acting features associated with RNA stability and find that RNAs that are upregulated across development tend to be more stable, while downregulated RNAs are less stable. To probe how disruption of RNA turnover impacts cortical development, we assess developmental requirements of CNOT3, a core component of the CCR4-NOT deadenylase complex. Mutations in CNOT3 are associated with human neurodevelopmental disorders, however its role in cortical development is unknown. Conditional knockout of Cnot3 in neural progenitors and their progeny in the developing mouse cortex leads to severe microcephaly due to reduced neuron production and p53-dependent apoptosis. Collectively, our findings demonstrate that fine-tuned control of RNA turnover is crucial for brain development.

neuroscience↗