Mice mutant for Egfr and Shp2 have defective cardiac semilunar valvulogenesis

Atrioventricular and semilunar valve abnormalities are common birth defects, but how cardiac valvulogenesis is directed remains largely unknown. During studies of genetic interaction between Egfr, encoding the epidermal growth factor receptor, and Ptpn11, encoding the protein-tyrosine-phosphatase Shp2, we discovered that Egfr is required for semilunar, but not atrioventricular, valve development. Although unnoticed in earlier studies, mice homozygous for the hypomorphic Egfr allele waved-2 (Egfrwa2/wa2) exhibit semilunar valve enlargement resulting from over-abundant mesenchymal cells. Egfr-/- mice (CD1 background) have similar defects. The penetrance and severity of the defects in Egfrwa2/wa2 mice are enhanced by heterozygosity for a targeted mutation of exon 2 of Ptpn11 (ref. 3). Compound (Egfrwa2/wa2:Ptpn11+/-) mutant mice also show premature lethality. Electrocardiography, echocardiography and haemodynamic analyses showed that affected mice develop aortic stenosis and regurgitation. Our results identify the Egfr and Shp2 as components of a growth-factor signalling pathway required specifically for semilunar valvulogenesis, support the hypothesis that Shp2 is required for Egfr signalling in vivo, and provide an animal model for aortic valve disease.     

Late Cenozoic high-resolution magnetostratigraphy in the Kunlun Pass Basin and its implications for the uplift of the northern Tibetan Plateau

The Kunlun Pass Basin, located in the middle of the eastern Kunlun Mountains, received relatively continuous late Cenozoic sediments from the surrounding mountains, archiving great information to understand the deformation and uplift histories of the northern Tibetan Plateau. The Kunlun-Yellow River Movement, identified from the tectonomorphologic and sedimentary evolution of the Kunlun Pass Basin by Cui Zhijiu et al. （1997, 1998）, is roughly coincident with many important global and Plateau climatic and environmental events, becoming a crucial time interval to understand tectonic-climatic interactions. However, the ages used to constrict the events remain great uncertainty. Here, we present the results of detailed magnetostratigraphy of the late Cenozoic sediments in the Kunlun Pass Basin, which show the basin sediments were formed between about 3.6 Ma and 0.5 Ma and the Kunlun-Yellow River Movement occurred at 1.2 to ～0.78 Ma. The lithology, sedimentary facies and lithofacies associations divide the basin into five stages of tectonosedimentary evolution, indicating the northern Tibetan Plateau having experienced five episodes of tectonic uplifts at ～3.6, 2.69-2.58, 1.77, 1.2, 0.87 and ～0.78 Ma since the Pliocene.