Angiogenic sprouting into neural tissue requires Gpr124, an orphan G protein-coupled receptor.

The vasculature of the CNS is structurally and functionally distinct from that of other organ systems and is particularly prone to developmental abnormalities and hemorrhage. Although other embryonic tissues undergo primary vascularization, the developing nervous system is unique in that it is secondarily vascularized by sprouting angiogenesis from a surrounding perineural plexus. This sprouting angiogenesis requires the TGF-ß and Wnt pathways because ablation of these pathways results in aberrant sprouting and hemorrhage. We have genetically deleted Gpr124, a member of the large family of long N-terminal group B G protein-coupled receptors, few members of which have identified ligands or well-defined biologic functions in mammals. We show that, in the developing CNS, Gpr124 is specifically expressed in the vasculature and is absolutely required for proper angiogenic sprouting into the developing neural tube. Embryos lacking Gpr124 exhibit vascular defects characterized by delayed vascular penetration, formation of pathological glomeruloid tufts within the CNS, and hemorrhage. In addition, they display defects in palate and lung development, two processes in which TGF-ß and/or Wnt pathways also play important roles. We also show that TGF-ß stimulates Gpr124 expression, and ablation of Gpr124 results in perturbed TGF-ß pathway activation, suggesting roles for Gpr124 in modulating TGF-ß signaling. These results represent a unique function attributed to a long N-terminal group B-type G protein-coupled receptor in a mammalian system.

Aspects of Dietary Diversity Changes across Adulthood in Racially Diverse Adults.

Knowledge of various aspects of dietary diversity (DD)-an essential healthful dietary component-across adulthood is limited. This study examined three DD aspects over time in racially diverse adults. Participants were from the National Institute on Aging, Healthy Aging in Neighborhoods of Diversity across the Life Span study. DD measures were calculated at baseline (N = 2177), and first and second examination follow-ups (N = 2140 and N = 2066, respectively) using two 24-h recalls. The count was based on the consumption of ≥50% of an equivalent from 21 food groups. Evenness was derived using the Berry-Index adjusted by the food's health value; dissimilarity, by Mahalanobis Distance. Mixed-effects linear regression models were conducted to test changes in DD across adulthood, adjusting for sex, race, poverty status and education as fixed effects, and adjusting for smoking, age and energy as time-dependent variables. Only dissimilarity showed significant interactions of time × race (p = 0.0005), and time × poverty status (p = 0.0325), indicating a slower rate of increase over time in dissimilarity scores among Whites compared with African-Americans and those with income >125% poverty versus <125% poverty. A significant interaction between time×energy (p < 0.0001) was noted for both evenness and dissimilarity scores. To our knowledge, this is the first study to document the differential change in dissimilarity scores by race and income over time.

Vascular endothelial tyrosine phosphatase (VE-PTP)-null mice undergo vasculogenesis but die embryonically because of defects in angiogenesis.

Development of the vascular system depends on the highly coordinated actions of a variety of angiogenic regulators. Several of these regulators are members of the tyrosine kinase superfamily, including VEGF receptors and angiopoietin receptors, Tie1 and Tie2. Tyrosine kinase signaling is counter-regulated by the activity of tyrosine phosphatases, including vascular endothelial protein tyrosine phosphatase (VE-PTP), which has previously been shown to modulate Tie2 activity. We generated mice in which VE-PTP is replaced with a reporter gene. We confirm that VE-PTP is expressed in endothelium and also show that VE-PTP is highly expressed in the developing outflow tract of the heart and later is expressed in developing heart valves. Vasculogenesis occurs normally in mice lacking VE-PTP; however, angiogenesis is abnormal. Angiogenic defects in VE-PTP-null mice were most pronounced in the yolk sac and include a complete failure to elaborate the primitive vascular scaffold into higher-order branched arteries, veins, and capillaries. VE-PTP continues to be expressed into adulthood in the vasculature and heart valves, suggesting later roles in vascular development or homeostasis. VE-PTP is also expressed in the vasculature of growing tumors, suggesting that VE-PTP may be a new potential target for angiogenic therapies.