Dand5, also known as COCO, encodes a protein that acts as an antagonist to Nodal/TGF-β and Wnt pathways [3]. It is well-known as the first asymmetric gene involved in vertebrate left-right (LR) development and plays a crucial role in maintaining the correct patterning of asymmetric internal organs, as well as in somite specification [1].

In zebrafish, dand5 -/- mutant embryos show that the asymmetric cues from the left-right organizer (LRO) are abolished, and the movement of Non-KV Sox17:GFP+ Tailbud Cells (NKSTCs) from the posterior cluster becomes bilaterally synchronous, affecting the expression patterns of myogenic factors and tail size [1]. In mouse embryonic stem cells, Dand5 loss-of-function generates more cardiac beating foci, upregulates early cardiac gene networks, and reduces genes involved in cardiomyocyte maturation [2]. DAND5-KO embryoid bodies progress faster through differentiation, with differences in genes related to Notch and Wnt signalling pathways, lower migratory rates, and higher concentrations of focal adhesions. In vivo, Dand5 depletion compromises correct valve structure [3]. In human-induced pluripotent stem cells, absence of DAND5 sustains the proliferation of cardiomyocytes and alters their electrophysiological maturation properties [5].

In conclusion, Dand5 is essential for vertebrate LR development, somite specification, and cardiac development. Gene-knockout models in zebrafish and mice have revealed its role in cell movement, cardiac differentiation, and EMT processes. Understanding Dand5 function may provide insights into congenital heart defects, heterotaxy syndrome, and potentially offer new therapeutic strategies for treating these diseases [1,2,3,4,5].