Hand1, also known as heart and neural crest derivatives expressed 1, is a basic Helix-loop-Helix transcription factor. It plays crucial roles in multiple biological processes, including heart development, trophoblast differentiation, and is associated with pathways like cell differentiation, localization, and cell projection organization [1,2,3,4]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In mouse models, conditional ablation of Hand1 in the embryonic myocardium using Nkx2.5Cre or αMhc-Cre drivers leads to morphological defects including cardiac conduction system defects, interventricular septal defects, and abnormal left ventricular papillary muscles, resulting in diastolic heart failure in adult mice, indicating its role in cardiomyocyte morphogenic patterning and maturation during embryogenesis [4]. In BeWo cells (a choriocarcinoma model of human cytotrophoblasts), HAND1 knockdown leads to down-regulation of 664 genes and up-regulation of 59 genes, disrupting pathways related to cell differentiation and organization, while in human placental microvascular endothelial cells, only seven genes are changed upon HAND1 knockdown [1].

In conclusion, Hand1 is essential for heart development and trophoblast function. The KO/CKO mouse models have revealed its role in congenital heart defects and placental-related pathologies, contributing to our understanding of these disease areas.