Simultaneous production of diverse neuronal subtypes during early corticogenesis
Posted on: 29 August 2018
Preprint posted on 16 July 2018
How does the amazing diversity of cortical neurons emerge during development? A new preprint suggests that during early stages distinct types are simultaneously produced, while later on neuronal production is homogenous and sequential.
Selected by Boyan BonevCategories: developmental biology, neuroscience
Why is it important?
The cerebral cortex contains many different neuronal subtypes with distinctive morphology, connectivity and gene expression. Abnormal cortical development often translates into prominent neurodevelopmental and neuropsychiatric diseases, which affect different neuronal subtypes. How these neurons are produced in a precise sequence during embryonic development is one of the key questions in developmental neuroscience. Despite intense research in this area, the molecular mechanisms regulating the progression of molecular competence in cortical progenitors and how neuronal subtypes are produced temporally are still not well understood.
What are the key findings?
In this preprint Magrinelli and colleagues examine the fate of simultaneously-born cohorts of neurons at multiple stages during cortical development. To accomplish this, they utilize a high temporal resolution labeling technique, called FlashTag, which they combine with chronic administration of BrdU to distinguish between direct versus indirect neurogenesis. Using this approach, they uncover that at early stages of corticogenesis, there is an unexpected diversity in the molecular identity, laminar position and connectivity of simultaneously-born neurons. Conversely, later during embryonic development, the production of neurons is much more homogenous. Using retrograde labeling, the authors show that molecular differences in early-born neurons are also ultimately translated into laminar fate and connectivity. Finally, the authors suggest that at least some of the molecular diversity is postmitotic, as markers of different subtypes are progressively acquired during differentiation.

Questions arising
How much molecular diversity is encoded already in neural progenitors versus acquired postmitotically?
What are the molecular mechanisms for the progressive restriction of fate potential during corticogenesis?
What is the contribution of epigenetic modifications and post-transcriptional regulation to lineage specification in the cortex?
Related Research
Vitali I., et. al. & Jabaudon D. Progenitor Hyperpolarization Regulates the Sequential Generation of Neuronal Subtypes in the Developing Neocortex. Cell (2018).
Govindan S. & Jabaudon D. Coupling progenitor and neuronal diversity in the developing neocortex. FEBS Lett (2017).
Yuzwa SA. et. al., & Miller FD. Developmental Emergence of Adult Neural Stem Cells as Revealed by Single-Cell Transcriptional Profiling. Cell Rep (2017)
Molyneaux B., Arlotta P., et al. & Macklis J. Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci (2007)
Telley, L., et al. Sequential Transcriptional Waves Direct the Differentiation of Newborn Neurons in the Mouse Neocortex. Science 351, 1443–6 (2016).
doi: https://doi.org/10.1242/prelights.4575
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