Ruecker, T. | Search bioRxiv

bioRxiv2026

Temporal Profiling of Upper-Layer Neurons Reveals Changes in the Molecular Landscape Upon Maternal Immune Activation

Neuronal differentiation is a dynamic, multi-layered process that transforms progenitor cells into functionally integrated neurons, yet the coordinated molecular programs underlying this transition remain incompletely understood. Here, we define the developmental trajectory of murine upper-layer cortical neurons using an integrated multi-omics approach combining transcriptomics and proteomics across key stages of neurogenesis. We find that neuronal identity emerges gradually through coordinated transitions from RNA processing and splicing programs toward synaptic and metabolic maturation. Integration of matched transcriptomic and proteomic datasets reveals a compact set of concordant molecular modules that define this trajectory, highlighting post-transcriptional regulation as a central driver of neuronal maturation. We further show that maternal immune activation (MIA), a model of prenatal inflammation, deranges this developmental program. MIA induces sustained upregulation of Wnt signalling pathways alongside a downregulation of synaptic regulators, without detectable global alterations in DNA methylation. These molecular changes are accompanied by defects in neuronal positioning during cortical development, linking altered molecular trajectories to functional outcomes. Together, our findings establish a temporal molecular framework of neuronal differentiation and demonstrate that prenatal environmental perturbations reshape cortical development primarily through post-transcriptional and signalling-based mechanisms.

neuroscience↗

bioRxiv2020

Centrosome-dependent microtubule organization sets the conditions for axon formation

Microtubule remodeling is critical during axon development when the more stable microtubules populate the axon. It is not completely understood, however, how this local cytoskeleton remodeling is coordinated. The centrosome, the main microtubule-organizing center (MTOC), has been suggested to be crucial for axon specification 1-5. Conversely, it was proposed that axon elongation is independent of centrosomal functions 6. Here we report that microtubule dynamics in early neurons follow a radial organization which establishes the conditions for the axon formation. Using high-resolution microscopy of early developing neurons, we demonstrate that few somatic acetylated microtubules are restricted near the centrosome. At later stages, however, acetylated microtubules spread out in the soma and concentrate in the growing axon. Furthermore, live-imaging of the microtubule plus-end binding protein EB3 in early differentiating neurons shows that growing microtubules have increased length and growth speed near the MTOC, suggesting local differences that might favor axon selection. Importantly, due to the lack of somatic stable/acetylated microtubules in early developing neurons, disruption of the F-actin cytoskeleton does not induce multiple axons, as it does at later stages of differentiation. Finally, we demonstrate that overexpression of the centrosomal protein 120 (Cep120), known for promoting microtubule acetylation and stabilization, induces multiple axons, while its downregulation decreases the content of proteins regulating microtubule dynamics and stability, hence hampering axon formation. Collectively, our data show that early centrosome-dependent microtubule organization contributes to axon formation.

cell biology↗