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Summary The Hairy-related transcription factor family of Notch- and ALK1-downstream transcriptional repressors, called Hrt/Hey/Hesr/Chf/Herp/Gridlock, has complementary and indispensable functions for vascular development. While mouse embryos null for either Hrt1/Hey1 or Hrt2/Hey2 did not show early vascular phenotypes, Hrt1/Hey1; Hrt2/Hey2 double null mice (H1ko/H2ko) showed embryonic lethality with severe impairment of vascular morphogenesis. It remained unclear, however, whether Hrt/Hey functions are required in endothelial cells or vascular smooth muscle cells. In this study, we demonstrate that mice with endothelial-specific deletion of Hrt2/Hey2 combined with global Hrt1/Hey1 deletion (H1ko/H2eko) show abnormal vascular morphogenesis and embryonic lethality. Their defects were characterized by the failure of vascular network formation in the yolk sac, abnormalities of embryonic vascular structures and impaired smooth muscle cell recruitment, and were virtually identical to the H1ko/H2ko phenotypes. Among signaling molecules implicated in vascular development, Robo4 expression was significantly increased and activation of Src family kinases was suppressed in endothelial cells of H1ko/H2eko embryos. The present study indicates an important role of Hrt1/Hey1 and Hrt2/Hey2 in endothelial cells during early vascular development, and further suggests involvement of Robo4 and Src family kinases in the mechanisms of embryonic vascular defects caused by the Hrt/Hey deficiency. genesis 52:897–906, 2014. © 2014 Wiley Periodicals, Inc.

The frequency of occurrence of minerals in 1876 samples of Sanbagawa pelitic schist in central Shikoku is summarized on the basis of microscopic observation accompanied, in part, by use of an electron microprobe. All samples contain quartz, plagioclase, phengite, chlorite and graphite. More than 90% of samples contain clinozoisite, titanite and apatite. Garnet is present in 95% of samples from the garnet zone, and biotite is present in 64% of samples from the albite-biotite zone. Calcite is found in about 40% of samples of the pelitic schist collected from outcrop, but occurs in 95% of the pelitic schist from drill cores. Calcite was apparently ubiquitous in the pelitic schist during the Sanbagawa metamorphism, but must have been dissolved recently by the action of surface or ground water. The mineral assemblages of the Sanbagawa pelitic schist have to be analyzed in the system with excess calcite, quartz, albite (or oligoclase), clinozoisite, graphite and fluid that is composed mainly of H2O, CO2 and CH4. In the presence of calcite, reactions that produce garnet, rutile, oligoclase, biotite and hornblende, some of which define isograds of the metamorphic belt, should be written as mixed volatile equilibria that tend to take place at lower temperature than the dehydration reactions that have been proposed. The presence of calcite in pelitic schist suggests that fluid composition is a variable as important in determining mineral assemblages as pressure and temperature. Thus Ca-bearing phases must be taken into account to analyze the phase relations of calcite-bearing pelitic schist, even if CaO content of Sanbagawa pelitic schist is low. As calcite is a common phase, the mineral assemblages of the biotite zone pelitic schist may contravene the mineralogical phase rule and warrant further study.