Biology subjects

Beckel, M. S.

Publications and source records attributed to Beckel, M. S..

3 recordsLinked to original sources

bioRxiv2025

Neuronal development shapes activity-dependent gene expression in a stimulus-specific manner

Neuronal activity-dependent gene expression is fundamental to a wide variety of brain functions. However, how development progress and stimulation modalities specifically affect neuron transcription is not fully understood. In this work, we first investigate the influence of development on neuronal firing and activity-driven transcription. We used an RNA sequencing approach over 7 days in vitro (DIV) or mature 21 DIV neurons, comparing neuronal depolarization with potassium chloride (KCl) versus Biccuculine application, a synaptic modality to induce neuronal activity. To further investigate how different activity patterns influence gene transcription in mature neurons, we compared global gene expression in neurons treated with three different and extensively used activation protocols: KCl, Bicuculine (Bic), and TTX withdrawal (TTXw). Our results demonstrate a strong influence of development on activity-dependent gene expression, and showed that different patterns of neuronal activity induce different transcriptional profiles and exhibit distinct temporal dynamics for the same genes. These findings offer novel insights into the complex relationship between neuronal activity and gene expression, shedding light on the context-dependent nature of activity-dependent transcriptional responses.

neuroscience↗

bioRxiv2024

Arabidopsis PRMT5 Buffers Pre-mRNA Splicing and Development Against Genetic Variation in Donor Splice Sites

Genetic variation at splice site signals significantly influences alternative splicing, leading to transcriptomic and proteomic diversity that enhances phenotypic plasticity and adaptation. However, novel splice variants can negatively impact gene expression and developmental stability. Canalization--the ability of an organism to maintain a consistent phenotype despite genetic or environmental variations--helps balance the effects of genetic variation on development and evolution. Protein arginine methyltransferase 5 (PRMT5) is a key splicing regulator in plants and animals. Most splicing changes in prmt5 mutants are linked to weak donor splice sites, suggesting that PRMT5 may buffer splicing against genetic variation. We examined PRMT5s effects on splicing and development in two genetically divergent Arabidopsis thaliana accessions with different single nucleotide polymorphisms (SNPs) affecting donor splice sites. While PRMT5 inactivation similarly affected splicing in both backgrounds, it significantly increased splicing and phenotypic differences between the accessions. Our findings suggest that PRMT5 contributes to canalization, mitigating the impact of splice site polymorphisms and facilitating the evolution of adaptive splicing patterns.

molecular biology↗

bioRxiv2023

Transcriptional dynamics orchestrating the development and integration of neurons born in the adult hippocampus

The adult hippocampus generates new granule cells (aGCs) that exhibit distinct functional capabilities along development, conveying a unique form of plasticity to the preexisting circuits. While early differentiation of adult radial glia-like neural stem cells (RGL) has been studied extensively, the molecular mechanisms guiding the maturation of postmitotic neurons remain unknown. Here, we used a precise birthdating strategy to follow newborn aGCs along differentiation using single-nuclei RNA sequencing (snRNA-seq). Transcriptional profiling revealed a continuous trajectory from RGLs to mature aGCs, with multiple sequential immature stages bearing increasing levels of effector genes supporting growth, excitability and synaptogenesis. Remarkably, four discrete cellular states were defined by the expression of distinct sets of transcription factors (TFs): quiescent neural stem cells, proliferative progenitors, postmitotic immature aGCs, and mature aGCs. The transition from immature to mature aCGs involved a transcriptional switch that shutdown molecular cascades promoting cell growth, such as the SoxC family of TFs, to activate programs controlling neuronal homeostasis. Indeed, aGCs overexpressing Sox4 or Sox11 remained stalled at the immature state. Our results unveil precise molecular mechanisms driving adult neural stem cells through the pathway of neuronal differentiation.

neuroscience↗