Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex

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Science  03 Mar 2016:
DOI: 10.1126/science.aad8361

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During corticogenesis, excitatory neurons are born from progenitors located in the ventricular zone (VZ), from where they migrate to assemble into circuits. How neuronal identity is dynamically specified upon progenitor division is unknown. Here, we study this process using a high temporal-resolution technology allowing fluorescent tagging of isochronic cohorts of newborn VZ cells. By combining this in vivo approach with single-cell transcriptomics in mouse, we identify and functionally characterize neuron-specific primordial transcriptional programs as they dynamically unfold. Our results reveal early transcriptional waves that instruct the sequence of neuronal differentiation events, guiding newborn neurons toward their final fate, and contribute to a roadmap for the reverse engineering of specific classes of cortical neurons from undifferentiated cells.

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