A major cause of the cerebral cortex expansion that occurred during evolution is the increase in subventricular zone (SVZ) progenitors. We found that progenitors in the outer SVZ (OSVZ) of developing human neocortex retain features of radial glia, in contrast to rodent SVZ progenitors, which have limited proliferation potential. Although delaminating from apical adherens junctions, OSVZ progenitors maintained a basal process contacting the basal lamina, a canonical epithelial property. OSVZ progenitor divisions resulted in asymmetric inheritance of their basal process. Notably, OSVZ progenitors are also found in the ferret, a gyrencephalic nonprimate. Functional disruption of integrins, expressed on the basal process of ferret OSVZ progenitors, markedly decreased the OSVZ progenitor population size, but not that of other, process-lacking SVZ progenitors, in slice cultures of ferret neocortex. Our findings suggest that maintenance of this epithelial property allows integrin-mediated, repeated asymmetric divisions of OSVZ progenitors, providing a basis for neocortical expansion.

The expansion of the neocortex during mammalian brain evolution results primarily from an increase in neural progenitor cell divisions in its two principal germinal zones during development, the ventricular zone (VZ) and the subventricular zone (SVZ). Using mRNA sequencing, we analyzed the transcriptomes of fetal human and embryonic mouse VZ, SVZ, and cortical plate. In mouse, the transcriptome of the SVZ was more similar to that of the cortical plate than that of the VZ, whereas in human the opposite was the case, with the inner and outer SVZ being highly related to each other despite their cytoarchitectonic differences. We describe sets of genes that are up-or down-regulated in each germinal zone. These data suggest that cell adhesion and cell-extracellular matrix interactions promote the proliferation and self-renewal of neural progenitors in the developing human neocortex. Notably, relevant extracellular matrix-associated genes include distinct sets of collagens, laminins, proteoglycans, and integrins, along with specific sets of growth factors and morphogens. Our data establish a basis for identifying novel cell-type markers and open up avenues to unravel the molecular basis of neocortex expansion during evolution.cerebral cortex | neural stem cells | neurogenesis N eocortex expansion is a hallmark of mammalian brain evolution. With regard to neuron number, a major cause of this expansion is the increase in the population size of neural stem and progenitor cells (NSPCs) and the number of divisions that each of the various NSPC types undergoes during cortical development (1-4). Two principal classes of these cells can be distinguished based on the location of their mitosis: (i) apical progenitors (APs), which undergo mitosis at the luminal surface of the ventricular zone (VZ); and (ii) basal progenitors (BPs), which undergo mitosis at an abventricular location, typically in the subventricular zone (SVZ) (2, 5, 6). Neurons born from AP and BP cell divisions migrate radially and settle at the basal (pial) side of the developing cortical wall to form the cortical plate (CP).Both APs and BPs comprise several types of NSPCs that differ in key cell biological features (e.g., cell polarity, cell processes, cell-to-cell junctions, nuclear migration) and in the principal modes of cell division (symmetric proliferative vs. asymmetric self-renewing vs. symmetric or asymmetric consumptive) (2, 5-10). APs comprise neuroepithelial cells, which transform into apical radial glial cells (aRGCs) at the onset of neurogenesis (11), and short neural precursors (12). BPs include basal (or outer) radial glial cells (bRGCs), transit amplifying progenitors (TAPs), and intermediate progenitor cells (IPCs) (2, 3, 13).The evolutionary expansion of the neocortex is associated with an increase in the thickness of the SVZ, which develops into two cytoarchitecturally distinct zones, an inner SVZ (ISVZ) and an outer SVZ (OSVZ) (1-4, 14, 15). The evolutionary increase in the SVZ is accompanied by a change in the proportion of BP subtypes. Fo...

These results confirm the poorer prognosis of obese women with early-stage breast cancer. Recurrence rates were lower for anastrozole than tamoxifen for all BMI quintiles. Our results suggest that the relative efficacy of anastrozole compared to tamoxifen is greater in thin postmenopausal women and higher doses or more complete inhibitors might be more effective in overweight women, but this requires independent confirmation.

The present study provides the first evidence for long-lasting effects of antenatal synthetic GC exposure on HPA-axis reactivity in term-born children. These findings may bear important implications regarding the vulnerability for stress-related physical and psychiatric disorders, for which dysregulation of the HPA-axis has been discussed as a potential causal factor.

Our data indicate that conditions related to a threatening preterm delivery rather than antenatal sGC treatment per se are associated with long-term decreases in the child's intelligence. Although these findings imply that a single course of sGC therapy does not aggravate long-term cognitive deficits, they highlight the need for interventions to reduce the detrimental consequences of distress induced by a threatening preterm delivery.