Temporal Regulation of Cortical Neurogenesis in Development and Evolution (360G-Wellcome-105358_Z_14_Z)

"The cerebral cortex is involved in a wide range of functions, from sensory processing and control of voluntary movement to language, thought and consciousness. Cortical neurons are produced during development in a temporally ordered progression from multipotent progenitor cells, with lower-layer neurons generated before upper-layer neurons. The molecular mechanisms regulating this temporal progression are not understood, although this process appears to be controlled largely by cell-intrinsic timing mechanisms that can be recapitulated in vitro. Notwithstanding considerable variation in cortical size and cellular components in different mammalian species, the temporal order of production of cortical neurons is evolutionarily conserved. The timing of this progression is however very different between species, scaling with body and cortical size; the cellular and molecular mechanisms underlying these evolutionary differences are currently unknown. This project will: (i) Characterise the molecular mechanism(s) of action of known lineage-progression regulators during human cortical development; (ii) Identify and characterise novel genes involved in regulating the temporal order of production of different cortical neuron subtypes during human development; (iii) Investigate and characterise any adaptations of the lineage-progression regulatory mechanism that might result in evolutionary differences in lineage-progression timing. "