Local generation of glia is a major astrocyte source in postnatal cortex

Abstract

A major source of glia in the postnatal cortex in mice is the local proliferation of differentiated astrocytes. Within weeks of birth, the population of astrocytes in the rodent brain increases by six to eight times. Although previous work suggested that progenitor-cell proliferation was responsible for this postnatal increase, this study finds evidence for local proliferation of astrocytes in the postnatal cortex during development. The resulting population of new cells integrates into the existing glial network, expanding the previous idea that only injury can trigger local proliferation. Glial cells constitute nearly 50% of the cells in the human brain1. Astrocytes, which make up the largest glial population, are crucial to the regulation of synaptic connectivity during postnatal development2. Because defects in astrocyte generation are associated with severe neurological disorders such as brain tumours3, it is important to understand how astrocytes are produced. Astrocytes reportedly arise from two sources4,5,6: radial glia in the ventricular zone and progenitors in the subventricular zone, with the contribution from each region shifting with time. During the first three weeks of postnatal development, the glial cell population, which contains predominantly astrocytes, expands 6–8-fold in the rodent brain7. Little is known about the mechanisms underlying this expansion. Here we show that a major source of glia in the postnatal cortex in mice is the local proliferation of differentiated astrocytes. Unlike glial progenitors in the subventricular zone, differentiated astrocytes undergo symmetric division, and their progeny integrate functionally into the existing glial network as mature astrocytes that form endfeet with blood vessels, couple electrically to neighbouring astrocytes, and take up glutamate after neuronal activity.