Histological characterization and development of mesial surface sulci in the human brain at 13-15 gestational weeks through high-resolution histology

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres. Of note at this stage, when most of the cerebrum is occupied by lateral ventricles and the corpus callosum is incompletely developed, we postulate that these mesial infolds represent the primordial stage of cingulate, callosal, and calcarine sulci, features of mesial cortical development. Our observations are based on the multimodal approach and further include histological three-dimensional reconstruction that highlights the importance of the plane of sectioning. We describe the laminar organization of the developing cortical mantle, including these infolds from the marginal to ventricular zone, with Nissl, hematoxylin and eosin, and glial fibrillary acidic protein (GFAP) immunohistochemistry. Despite the absence of major sulci on the dorsal surface, the boundaries among the orbital, frontal, parietal, and occipital cortex were very well demarcated, primarily by the cytoarchitecture differences in the organization of the subplate (SP) and intermediate zone (IZ) in these locations. The parietal region has the thickest cortical plate (CP), SP, and IZ, whereas the orbital region shows the thinnest CP and reveals an extra cell-sparse layer above the bilaminar SP. The subcortical structures show intensely GFAP-immunolabeled soma, absent in the cerebral mantle. Our findings establish a normative neurodevelopment baseline at the early stage. We report developing patterns of early sulci, calcarine and cingulate on the mesial surface, at the cellular level, observed in the sagittal plane in 13-15 gestational week fetal brain. High-resolution histological findings are supported by postmortem MRI, Blockface imaging, and 3D reconstruction of histological sections that allow comparison in the orthogonal planes. This study describes the cytoarchitectural organization of the developing cerebral cortex, using serial sections from the whole fetal brain in the early fetal stage. image