Progenitor cells that generate neuron pairs ("pair progenitor cells") are implicated in mammalian cortical development, and their division has been thought to be "symmetric." However, asymmetric growth of two sister neurons generated by the division of a pair progenitor cell would lead to more efficient generation of neuronal diversity in the cortex. To explore mechanisms by which pair progenitor cells provide neuronal diversity, we examined molecular differences between a pair of neurons generated in clonal-density culture. Time-course analysis for the acquisition of neuronal markers and the disappearance of Pax6 and Neurogenin2 (Ngn2) demonstrated that 1) these transcription factors are expressed transiently in some but not all young neurons and 2) some neuron pairs showed uneven/asymmetric expression of Pax6 (19.5%) or Ngn2 (23.8%), whereas other pairs were either symmetrically positive or negative. Asymmetric Pax6 distribution in neuron pairs was not associated with asymmetric distribution of Numb, which raises an intriguing possibility, that Pax6 asymmetry in neuron pairs is produced by an alternative mode of the cell autonomous mechanisms. Stage-dependent changes were noted in the pattern of Ngn2 retention in daughter neurons, reflecting qualitative changes in the pair progenitor population. We suggest that pair progenitor cells contribute to the generation of neuronal diversity through cell-intrinsic heterogeneity and asymmetric division.
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