Use of Frogs as a Model to Study the Etiology of HLHS

Abstract

A frog is a classical model organism used to uncover processes and regulations of early vertebrate development, including heart development. Recently, we showed that a frog also represents a useful model to study a rare human congenital heart disease, hypoplastic left heart syndrome. In this review, we first summarized the cellular events and molecular regulations of vertebrate heart development, and the benefit of using a frog model to study congenital heart diseases. Next, we described the challenges in elucidating the etiology of hypoplastic left heart syndrome and discussed how a frog model may contribute to our understanding of the molecular and cellular bases of the disease. We concluded that a frog model offers its unique advantage in uncovering the cellular mechanisms of hypoplastic left heart syndrome; however, combining multiple model organisms, including frogs, is needed to gain a comprehensive understanding of the disease.

Keywords: congenital heart disease; frog; hypoplastic left heart syndrome.

Figure 1

Ets1 knockdown in the cardiogenic mesoderm leads to HLHS-like phenotype in the frog. Transverse sections through (A) wildtype, (B) neural crest knockdown, and (C) cardiac mesoderm knockdown embryos are shown. Ets1 knockdown in the neural crest cells results in outflow tract defects but does not affect ventricular development significantly. In contrast, Ets1 knockdown in the cardiac mesoderm results in an underdeveloped ventricle with reduced chamber volume, mimicking the HLHS phenotype. SS, siral septum; OFT, outflow tract; V, ventricle. Scale bar = 200 um. (Reproduced with permission from [56].).