The Hey family of bHLH transcription factors are direct targets of Notch signaling. HEY2 (gridlock) is an important determinant of mammalian heart development, loss of which in mouse leads to cardiac defects with high postnatal lethality. Mouse Hey1 knockouts have no apparent phenotypic defect but the combined loss of Hey1 and Hey2 results in embryonic death after embryonic day 9.5 (E9.5) with a global lack of vascular remodeling and massive hemorrhage. Similar defects are observed in Jagged1 and Notch1 knockout mice.
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