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The origins of neuronal diversity in the developing mouse brain

May 09, 2019

They way neural progenitor cells produce more daughter cells, of different types, shifts with the individual neuroprogenitor's development, according to a new study of mouse brains. It relied on a relatively new neuron-labeling technology known as FlashTag (FT). The study shows that instead of always producing more of the same cells, as a neuroprogenitor transitions to new states within embryonic development, it produces daughter neurons that reflect those new states, too. The results reveal a fundamental mechanism underlying the generation of neuronal diversity in the rapidly developing brains of embryonic mice. During early corticogenesis (formation of the cerebral cortex), apical progenitor (AP) cells located in the brain's ventricular zone differentiate to become different types of neurons and begin to form the various neural circuits crucial for cognitive and sensorimotor function. In the adult brain, the type of neuron a neuroprogenitor becomes is determined by the interaction between progenitor-derived genetic information and environmentally-derived signals. However, in the developing brain, the factors driving the type of neuron that is produced remain elusive. One reason for this has been the lack of a technique allowing the precise dissection of neuronal cell states in specific cell types. Here, the researchers overcome this limitation by using FlashTag (FT), a method they had previously developed to label APs and their daughter neurons. Using FT to label mouse brain neuroprogenitors and high-temporal resolution single-cell RNA sequencing to study them at different embryonic stages, Ludovic Telley and colleagues surveyed early neurogenesis in embryonic mice. The approach allowed Telley et al. to identify and trace the transcriptional trajectory of APs and their daughter neurons at specific points during neocortex development. The study revealed a core set of temporally patterned genes that drive a shift in the fate of APs to reflect specific stages of neocortex development. According to the results, temporally dynamic molecular "birthmarks" are transmitted from mother to daughter cells, which influences the types of neurons they will become. As such, embryonic age-dependent transcriptional states of APs seed the neuronal diversity in the neocortex.
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American Association for the Advancement of Science

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