Genetic influence on neurogenesis in the dentate gyrus of adult mice

To address genetic influences on hippocampal neurogenesis in adult mice, we compared C57BL/6, BALB/c, CD1(ICR), and 129Sv/J mice to examine proliferation, survival, and differentiation of newborn cells in the dentate gyrus. Proliferation was highest in C57BL/6; the survival rate of newborn cells was highest in CD1. In all strains ≈60% of surviving newborn cells had a neuronal phenotype, but 129/SvJ produced more astrocytes. Over 6 days C57BL/6 produced 0.36% of their total granule cell number of 239,000 as new neurons, BALB/c 0.30% of 242,000, CD1 (ICR) 0.32% of 351,000, and 129/SvJ 0.16% of 280,000. These results show that different aspects of adult hippocampal neurogenesis are differentially influenced by the genetic background.

The transcription factor EPAS-1/hypoxia-inducible factor 2α plays an important role in vascular remodeling

We have studied the role of the basic helix–loop–helix–PAS transcription factor EPAS-1/hypoxia-inducible factor 2α in vascular development by gene targeting. In ICR/129 Sv outbred background, more than half of the mutants displayed varying degrees of vascular disorganization, typically in the yolk sac, and died in utero between embryonic day (E)9.5 and E13.5. In mutant embryos directly derived from EPAS-1−/− embryonic stem cells (hence in 129 Sv background), all embryos developed severe vascular defects both in the yolk sac and embryo proper and died between E9.5 and E12.5. Normal blood vessels were formed by vasculogenesis but they either fused improperly or failed to assemble into larger vessels later during development. Our results suggest that EPAS-1 plays an important role at postvasculogenesis stages and is required for the remodeling of the primary vascular network into a mature hierarchy pattern.