Decoding mixed messages in the developing cortex: translational regulation of neural progenitor fate

Regulation of stem cell fate decisions is elemental to faithful development, homeostasis, and organismal fitness. Emerging data demonstrate pluripotent stem cells exhibit a vast transcriptional landscape, which is refined as cells differentiate. In the developing neocortex, transcriptional priming of neural progenitors, coupled with post-transcriptional control, is critical for defining cell fates of projection neurons. In particular, radial glial progenitors exhibit dynamic post-transcriptional regulation, including subcellular mRNA localization, RNA decay, and translation. These processes involve both cis- regulatory and trans-regulatory factors, many of which are implicated in neurodevelopmental disease. This review highlights emerging post-transcriptional mechanisms which govern cortical development, with a particular focus on translational control of neuronal fates, including those relevant for disease.

Automated summary

Regulation of stem cell fate decisions is crucial for development, homeostasis, and organismal fitness. Transcriptional priming of neural progenitors and dynamic post-transcriptional regulation, particularly in radial glial progenitors, play a vital role in defining cell fates and are implicated in neurodevelopmental disease. Post-transcriptional mechanisms, including subcellular mRNA localization, RNA decay, and translation, are highlighted in governing cortical development and translational control of neuronal fates.