Active Genetics & Molecular Biology Brain & Nervous System

Translational regulation of cerebral cortex wiring

In plain English

AI plain-English summary

A mouse embryo’s developing brain builds its neural circuits by controlling when and where individual neurons translate genetic instructions into proteins, not just by switching genes on or off. Scientists know that neurons use dedicated genetic programs to wire the cerebral cortex—the brain’s outer layer responsible for complex behaviour—but they have largely overlooked the role of post-transcriptional regulation, the steps that occur *after* a gene is copied into RNA. This project asks whether two specific post-transcriptional processes—chemical modifications to messenger RNA and the specialisation of ribosomes (the cell’s protein factories)—fine-tune which proteins each neuron makes, and when, to ensure that billions of cells connect correctly during early development. Without this layer of control, the cortex may wire imprecisely, potentially underpinning neurodevelopmental conditions such as autism or epilepsy. This is fundamental science. It will not produce a treatment or diagnostic tomorrow. But understanding how translation shapes cortical wiring could eventually reveal why certain genetic mutations that affect RNA modification or ribosome function lead to brain disorders—and point toward molecular targets for intervention. Past work on post-transcriptional regulation in other contexts, for example, has already reshaped cancer therapy; similar principles may one day apply to the developing brain.

View original technical description
The mammalian cerebral cortex is a highly complex brain structure containing a wide diversity of neuronal cell types interconnected in a remarkably specific manner. The many behaviours observed in mammals rely on the precise assembly and fine-tuning of this connectivity, so understanding the molecular mechanisms that govern its development is a major scientific challenge. Neurons use dedicated transcriptional programmes to establish their connectivity, but in eukaryotes, post-transcriptional events control gene expression patterns and mediate key regulatory steps to eventually dictate cell function. However, it is yet unclear to what extent post-transcriptional mechanisms are involved in the formation of cortical networks. The goal of this proposal is to investigate the role of translation regulation in establishing neuronal connectivity during mouse cortical development, by studying two major processes that coordinate an effective and specialised translation: mRNA modifications and ribosome specialisation. We will address how these processes are differentially regulated in neuronal cell types for their integration into cortical networks, and how they are temporally regulated by changes in cortical dynamics during critical postnatal developmental stages. This will highlight how the refinement of transcriptional programmes by translation instructs cortical connectivity development.

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Researchers

Clémence Bernard (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Regulation of neuronal gene expression through chromosome architecture
Regulated mRNA stability and translation in neural stem cell development
Activity dependence and species effects in rodent and human local cortical wiring rules
Elucidating novel post-transcriptional regulatory mechanisms in neural development
MicroRNA control of local synaptic protein synthesis in neuronal dendrites

Original classification

Career Development Award

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