A sublethal ATP11A mutation associated with neurological deterioration causes aberrant phosphatidylcholine flipping in plasma membranes.

ATP11A translocates phosphatidylserine (PtdSer), but not phosphatidylcholine (PtdCho), from the outer to the inner leaflet of plasma membranes, thereby maintaining the asymmetric distribution of PtdSer. Here, we detected a de novo heterozygous point mutation of ATP11A in a patient with developmental delays and neurological deterioration. Mice carrying the corresponding mutation died perinatally of neurological disorders.

Gene expression profiling of neural stem cells and identification of regulators of neural differentiation during cortical development.

During mammalian brain development, neural stem cells transform from neuroepithelial cells to radial glial cells and finally remain as astrocyte-like cells in the postnatal and adult brain. Neuroepithelial cells divide symmetrically and expand the neural stem cell pool; after the onset of neurogenesis, radial glial cells sequentially produce deep layer neurons and then superficial layer neurons by asymmetric, self-renewing divisions during cortical development. Thereafter, gliogenesis supersedes neurogenesis, while a subset of neural stem cells retain their stemness and lurk in the postnatal and adult brain.