Distribution and Morphology of GFAP-Positive Astrocytes in the Human Fetal Brain at Second Trimester

Abstract

Background: Various studies have shown that a close physical and functional relationship exists between astrocytes and microglia during development. The maturation of astrocytes can be followed by their specific expression of glial fibrillary acidic protein (GFAP). Although there have been several reports on the expression of GFAP in the developing brain, these are mainly descriptive and have not defined clearly the regional distribution patterns of these cells during fetal development. Aim: This study set out to analyse the regional distribution and morphology of GFAP-expressing astrocytes during the latter half of the second trimester (19–23 gestational weeks) within five normal fetal brains, with a view towards comparing the findings with the microglial distribution and differentiation previously recorded throughout the same period. Results: A clear account of the morphology and regional distribution of GFAP-positive astrocytes is presented. Differentiating astrocytes (including radial glia and their processes) were found in the germinal layers, corpus callosum and cavum septum pellucidum, within neural tracts and surrounding the basal ganglia – areas known to be populated by microglia during the same period. The differentiation of astrocytes was predominant within the subplate and intermediate zone towards the end of the second trimester. Importantly, the differentiation of astrocytes within these regions followed a similar spatially interspersed pattern as reported for fetal microglia. However, astrocytes appeared to differentiate at a later stage within these regions than described for microglia. This will require further investigations for confirmation. Differentiated astrocytes were also found to associate with cortical blood vessels in a region-specific manner during the second trimester. Conclusions: These observations indicate that the differentiation and spatial distribution of astrocytes parallels those of microglia during the second trimester. It remains to be seen whether factors released by microglia can directly influence the differentiation of astrocytes in situ during development.

Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain

“…3I) of the glial wedge begin to differentiate into astrocytes (Fig. 3L) beginning at 14 gestational weeks and continuing until at least 19 gestational weeks in our study and up to 23 weeks as previously reported (Rezaie et al, 2003). sections, rostral is to the left.…”

“…In humans, immunostaining using GFAP antibody revealed bilateral structures on both sides of the corpus callosum corresponding to the GW and the IGG (Fig. 3), which confirms the findings of Lent et al (2005), who also identified the presence of these structures in the human embryonic brain, and those of Rezaie et al (2003), who analyzed GFAP staining in human fetuses between 19 and 23 weeks. In addition, Northern blot analysis demonstrates that both Slit2, which is secreted by the GW and IGG, and its axonal receptor Robo1 are expressed in the fetal brain at 17 gestational weeks (Fig.…”

“…In order to determine whether important midline structures shown to play key roles in regulating commissural development in mouse are also present in the developing human brain, a series of immunohistochemical assays were performed on coronal sections from human embryonic brains ranging from 13 to 19 weeks of gestation [a previous complimentary study utilized brains from 19 -23 weeks (Rezaie et al, 2003)]. Specific antibodies against the midline glial populations (the GW and IGG), the subcallosal sling, and the pioneering axons of the corpus callosum were utilized to determine whether these structures are present during human development.…”

Primary Mixed Glial Cultures from Fetal Ovine Forebrain Are a Valid Model of Inflammation-Mediated White Matter Injury

“…A second population of stellate-shaped astrocytes was also present, characterized by small somata and long branched processes. Both of these observations are consistent with type 1 (protoplasmic astrocytes) and type 2 (fibrous astrocytes), respectively [32,33]. …”

Physiological roles of microglia during development

“…2011). In the human developing telencephalon, the differentiation of astrocytes takes place predominantly in the subplate and the intermediate zone towards the end of the second trimester of pregnancy (Rezaie et al. 2003).…”