Cortical Interlaminar Astrocytes Are Generated Prenatally, Mature Postnatally, and Express Unique Markers in Human and Nonhuman Primates

Abstract

Interlaminar astrocytes (ILAs) are a subset of cortical astrocytes that reside in layer I, express GFAP, have a soma contacting the pia, and contain long interlaminar processes that extend through several cortical layers. We studied the prenatal and postnatal development of ILAs in three species of primates (rhesus macaque, chimpanzee, and human). We found that ILAs are generated prenatally likely from radial glial (RG) cells, that ILAs proliferate locally during gestation, and that ILAs extend interlaminar processes during postnatal stages of development. We showed that the density and morphological complexity of ILAs increase with age, and that ILAs express multiple markers that are expressed by RG cells (Pax6, Sox2, and Nestin), specific to inner and outer RG cells (Cryab and Hopx), and astrocyte markers (S100β, Aqp4, and GLAST) in prenatal stages and in adult. Finally, we demonstrated that rudimentary ILAs in mouse also express the RG markers Pax6, Sox2, and Nestin, but do not express S100β, Cryab, or Hopx, and that the density and morphological complexity of ILAs differ between primate species and mouse. Together these findings contribute new information on astrogenesis of this unique class of cells and suggest a lineal relationship between RG cells and ILAs.

Implication of cerebral astrocytes in major depression: A review of fine neuroanatomical evidence in humans

“…Golgi staining reveals the entire coarse morphology of astrocytes, but stains at random, and so cannot reveal astrocyte densities in the human brain. Golgi studies identified interlaminar astrocytes, a cortical astrocyte subtype with a unique morphology and molecular profile in the human and non‐human primate cortex (Colombo & Reisin, 2004; Falcone et al, 2020). Golgi studies also led to the hypothesis that human astrocyte morphology has physiological relevance, as astrocyte volume was found—much like the conductive properties of neuronal axons—to adhere to a length constant, that may maintain their potassium buffering and metabolic capacity with respect to cell size (Reichenbach, Siegel, Senitz, & Smith, 1992; Siegel et al, 1991).…”

Redefining varicose projection astrocytes in primates

“…VP-As also expressed the stem cell markers Cryab and HOPX, which label inner and outer radial glia during prenatal development (Figure 3c-e). We have previously shown that ILAs express each of these markers (Falcone et al, 2021).…”

Astrocytes in Alzheimer´s Disease: Pathological Significance and Molecular Pathways

“…Interlaminar astrocytes do not occupy specific territorial domains and overlap with their neighbours. They express markers of radial glia (Pax6, Sox2, and Nestin), as well as astrocytic markers GFAP, S100β, Aqp4, and GLAST in both rodents and hominids (Falcone et al 2021). Grafting human iPSC-derived astrocyte progenitors in the mouse brain results in appearance of GFAP-positive interlaminar astrocytes in layer I of the mouse cortex ( Fig.…”

“…Interlaminar astrocytes are almost exclusively found in higher primates (although there are descriptions of rudimentary interlaminar astrocytes in mouse (Falcone et al 2021)), and emerge at postnatal stages. Their somata are located in layer I of the cerebral cortex.…”