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Protein translation rate determines neocortical neuron fate

ABSTRACT: The mammalian neocortex comprises an enormous diversity regarding cell types, morphology, and connectivity. In this work, we discover a post-transcriptional mechanism of gene expression regulation, protein translation, as a determinant of cortical neuron identity. We find specific upregulation of protein synthesis in the progenitors of later-born neurons and show that translation rates and concomitantly protein half-lives are inherent features of cortical neuron subtypes. In a small molecule screening, we identify Ire1a as a regulator of Satb2 expression and neuronal polarity. In the developing brain, Ire1a regulates global translation rates, coordinates ribosome traffic, and the expression of eIF4A1. Furthermore, we demonstrate that the Satb2 mRNA translation requires eIF4A1 helicase activity towards its 5’-untranslated region. Altogether, we show that cortical neuron diversity is generated by mechanisms operating beyond gene transcription, with Ire1a-safeguarded proteostasis serving as an essential regulator of brain development.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebral Cortex

SUBMITTER: David Meierhofer

LAB HEAD: Mateusz Ambrozkiewicz

PROVIDER: PXD048919 | Pride | 2025-04-15

REPOSITORIES: Pride

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			Action	DRS
	E12_IP_Puro_1.raw	Raw
	E12_IP_Puro_2.raw	Raw
	E12_IP_Puro_3.raw	Raw
	E12_IP_Puro_CHX.raw	Raw
	E12_Puro_CHX.raw	Raw

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Protein translation rate determines neocortical neuron fate

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