Gastrulation-stage gene expression in mouse embryos foreshadows the development of syndromic birth defects.

In animal models, deficiency phenocopies gene expression changes and birth defects seen in Cornelia de Lange syndrome, the most common cause of which is haploinsufficiency. Previous studies in mice suggested that heart development is abnormal as soon as cardiogenic tissue is formed. To investigate this, we performed single-cell RNA sequencing on wild-type and mouse embryos at gastrulation and early cardiac crescent stages. embryos had fewer mesoderm cells than wild-type and altered proportions of mesodermal cell subpopulations. These findings were associated with underexpression of genes implicated in driving specific mesodermal lineages. In addition, was found to be overexpressed in all germ layers, and many gene expression changes observed in embryos could be attributed to overexpression. These findings establish a link between deficiency, overexpression, and gene expression dysregulation/lineage misallocation, which ultimately manifest as birth defects in animals and Cornelia de Lange syndrome.