Figure 3.

Developmental dynamics of microglia in the cortex

(A) Representative laminar structure of the developing cortex with its transient zones observed from CS23 (9^th pcw) in humans and representative cortical columns from 10 to 12 pcw showing (1) the development of the pre-subplate to the subplate at 12.5 pcw and the alignment of microglial cells at the CP-PSP/SP boundary and (2) the distribution of microglial cells across transient zones. Scale bars: 2 mm (left); 100 μm (right).

(B) Corrected microglial densities (against fold change in frontal telencephalic wall thickness with age) and proliferative dynamics in the telencephalon during development (CS10 [late 3^rd/early 4^th pcw]) until term (38 pcw) (n = 50). ^∗n/k, not known. Embryonic and early fetal temporal windows are most significant for proliferation against other temporal windows, while the early fetal window is the most significant against other temporal windows.

(C) Equally spaced temporal windows for proliferation levels (top) and densities (bottom) around the most significant first wave. Data are represented as mean ± SEM.

(D) Mean apoptotic index around the first peak of densities (n = 15, 8 cases between 7 and 11 pcw and 7 cases between 12 and 16 pcw) (top panel). Data are represented as mean ± SEM. Representative microglial cell death photomicrographs observed in wave 1 following the decrease in densities (bottom panel, black arrows in B). Scale bars: 20 μm.

(E) Migratory profile of microglia and type of migration in representative cases from the telencephalon (n = 12).

(F) Representative profile (top panel) of TMEM119⁺ and IBA1⁺ cell densities around the first significant density wave (10–16 pcw) (n = 6). Mean TMEM119⁺ and IBA1⁺ cell densities across the prenatal period (10–28 pcw, n = 10) (bottom panel). Data are shown as mean ± SEM.

(G) Ratio of labeled TMEM119⁺/IBA1⁺ cells during the prenatal period (10–28 pcw, n = 10). Data are presented as mean ±SEM.

(H) Representative confocal images of TMEM119⁺ cells in the MZ and the VZ of a 13-pcw case (left) and double labeling of TMEM119/IBA1 in bright field in a neocortical column at 13 pcw observed in the MZ (right). Scale bars (left): 50 μm; scale bars (right): 100 μm.

(I) Wave 2 microglial cell death at 18 and 23 pcw. Scale bars: 20 μm.

(J) Non-microglial death observed in the GE and in cortical transient zones at CS23 (9^th pcw) (top, scale bars: 100 μm) and at 24 pcw (bottom, scale bars: 50 μm).

(K) Proliferative dynamics and densities by sex across human development shown as relative cumulative frequency distribution plots (top panel) and mean values between the sexes (27M:23F) (bottom panel). Data are shown as mean ± SEM. R, right; L, left; CP, cortical plate; GE, ganglionic eminence; IZ, intermediate zone; M, meninges; MZ, marginal zone; PSP, pre-subplate; SP, subplate; SVZ, subventricular zone; VZ, ventricular zone. For all panels, asterisks represent adjusted p value significance as follows: ^∗p < 0.05, ^∗∗p < 0.001, ^∗∗∗p < 0.0001, and ns p > 0.05.