Abstract
Knowledge on cortical development is based mainly on rodents besides primates and carnivores, all being altricial. Here, we analyzed a precocial animal, the pig, looking at dorsoparietal cortex from E45 to P90. At E45, most ionized calcium-binding adapter molecule 1-positive (Iba1+) cells had a macrophage-like morphology and resided in meninges and choroid plexus. Only a few cells were scattered in the ventricular and subventricular zone (VZ and SVZ). At E60/E70, all laminar compartments displayed microglia cells at a low-to-moderate density, being highest in VZ and SVZ followed by intermediate zone/white matter (IZ/WM). The cortical plate and marginal zone displayed only a few Iba1+ cells. Cells were intensely labeled, but still had poorly arborized somata and many resembled ameboid, macrophage-like microglia. Concurrent with a massive increase in cortical volume, microglia cell density increased until E85, and further until E100/E110 (birth at E114) to densities that resemble those seen postnatally. A fraction of microglia colabeled with Ki67 suggesting proliferation in all laminar compartments. Cell-to-cell distance decreased substantially during this time, and the fraction of microglia to all nuclei and to neurons increases in the laminar compartments. Eventually, of all cortical DAPI+ nuclei 7-12% were Iba1+ microglia. From E70 onwards, more and more cells with ramified processes were present in MZ down to IZ/WM, showing, for instance, a close association with NeuN+, NPY+, and GAD65/67+ somata and axon initial segments. These results suggested that the development of microglia cell density and morphology proceeds rapidly from mid-gestation onwards reaching near-adult status already before birth.