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A Novel Ex vivo Culture Method for the Embryonic Mouse Heart
Published on: May 24, 2013
Use of whole embryo culture for studying heart development
Calvin T Hang1, Ching-Pin Chang
1Department of Medicine, Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Insights
Whole embryo culture is a powerful technique for studying congenital heart defects and cardiac diseases. This method allows direct drug application to embryos, aiding in the development of new therapeutics.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Embryology
Background:
- Congenital heart defects affect ~1% of newborns, causing significant infant and child mortality.
- Adult cardiac diseases often stem from developmental origins, like heart valve malformations.
- Understanding embryonic cardiac development is crucial for preventing and treating heart diseases.
Purpose of the Study:
- To describe a simplified whole embryo culture method for studying cardiac development.
- To highlight the advantages of ex utero embryo culture for drug screening and mechanistic studies.
- To facilitate research into the molecular pathways of heart formation and disease.
Main Methods:
- Utilizing whole embryo culture to grow midgestation embryos ex utero.
- Directly applying drugs or chemicals to cultured embryos for hypothesis testing.
- Performing pharmacological rescue experiments without genetic manipulation.
Main Results:
- Whole embryo culture enables direct drug intervention, bypassing maternal circulation and placental barriers.
- This method allows for easier control of drug dosage and pharmacokinetics.
- It is applicable for studying drug effects that might be compromised by placental function.
Conclusions:
- Whole embryo culture is a versatile and accessible tool for investigating cardiac development and disease.
- The technique is valuable for identifying therapeutic targets and understanding disease mechanisms.
- This simplified method can be implemented in standard laboratory settings.
Abstract:
Congenital heart defects occur in approximately 1% of newborns and are a major cause of morbidity and mortality in infants and children. Many adult cardiac diseases also have developmental basis, such as heart valve malformations, among others. Therefore, dissecting the developmental and molecular mechanisms underlying such defects in embryos is of great importance in prevention and developing therapeutics for heart diseases that manifest in infants or later in adults. Whole embryo culture is a valuable tool to study cardiac development in midgestation embryos, in which ventricular chambers are specified and expand, and the myocardium and endocardium interact to form various cardiac structures including heart valves and trabecular myocardium (Cell 118: 649-663, 2004; Dev Cell 14: 298-311, 2008). This technique is essentially growing a midgestation embryo ex utero in a test tube. One of the strengths of embryo culture is that it allows an investigator to easily manipulate or add drugs/chemicals directly to the embryos to test specific hypotheses in situations that are otherwise very difficult to perform for embryos in utero. For instance, embryo culture permits pharmacological rescue experiments to be performed in place of genetic rescue experiments which may require generation of specific mouse strains and crosses. Furthermore, because embryos are grown externally, drugs are directly acting on the cultured embryos rather than being degraded through maternal circulation or excluded from the embryos by the placenta. Drug dosage and kinetics are therefore easier to control with embryo culture. Conversely, drugs that compromise the placental function and are thus unusable for in utero experiments are applicable in cultured embryos since placental function is not required in whole embryo culture. The applications of whole embryo culture in the studies of molecular pathways involved in heart valve formation, myocardial growth, differentiation, and morphogenesis are demonstrated previously (Cell 118: 649-663, 2004; Dev Cell 14: 298-311, 2008; Nature 446: 62-67, 2010). Here we describe a method of embryo culture in a common laboratory setting without using special equipments.

