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Heart valve disease is a major clinical problem worldwide. Cardiac valve development and homeostasis need to be precisely controlled. Hippo signaling is essential for organ development and tissue homeostasis, while its role in valve formation and morphology maintenance remains unknown. VGLL4 is a transcription cofactor in vertebrates and we found it was mainly expressed in valve interstitial cells at the post-EMT stage and was maintained till the adult stage. Tissue specific knockout of VGLL4 in different cell lineages revealed that only loss of VGLL4 in endothelial cell lineage led to valve malformation with expanded expression of YAP targets. We further semi-knockout YAP in VGLL4 ablated hearts, and found hyper proliferation of arterial valve interstitial cells was significantly constrained. These findings suggest that VGLL4 is important for valve development and manipulation of Hippo components would be a potential therapy for preventing the progression of congenital valve disease.
We provide the first distribution pattern of the Microhyla heymonsi group based on available molecular and morphological data collected from East and Southeast Asia. Our analyses show a high level of genetic diversity in the M. heymonsi group with nine distinct lineages from China, Myanmar, Vietnam, Laos, Malaysia, Thailand, Cambodia, as well as Singapore, and Indonesia. The study also reveals the discovery of two new species in Vietnam, Microhyla hmongorum sp. nov. from Lai Chau Province and Microhyla xodangorum sp. nov. from Kon Tum Province. When comparing the 12S–16S rRNA gene, the genetic divergence between Microhyla xodangorum and other congeners of the Microhyla heymonsi group ranges from 7.5-- to 8.9% (M. cf. heymonsi) and approximately 8.4% between the new species and M. heymonsi s. str. from Taiwan, China. The genetic divergence between Microhyla hmongorum and its congeners ranges from 4.5–5.6% (M. cf. heymonsi) to 8.7% (Microhyla xodangorum). These new findings bring the total number of known species in the genus Microhyla to 48 and the recorded species of Microhyla from Vietnam to 14.