Scientists at the Francis Crick Institute in London have shown the earliest known stage in mammalian heart development.
Gastrulation is a crucial step in embryo formation that takes place during week three of pregnancy in humans. In this process, the blastocyst is re-organised into a multi-layered structure that contains the first three primary types of tissue: ectoderm, endoderm and mesoderm. The study published in PLOS Biology identifies that all four chambers of the heart originate from the mesoderm but at different times and from different locations. The first set of cells create the left ventricle, followed by cells forming the right ventricle and finally the two atria.
Professor Sir Jim Smith, one of the senior authors of the study, is hoping this will provide insight into the origin of heart defects: 'Investigating how different types of cells in an embryo form at the right time and in the right place is crucial for understanding why this can sometimes go wrong. Congenital heart diseases affect around one in 180 babies worldwide and work like ours may help explain why just a single chamber of the heart is affected in heart defects such as left ventricle hypoplasia.'
To visualise the development process the researchers used mouse embryos and observed them under high-resolution microscopes by tracing of Foxa2, a transcription factor that is crucial during gastrulation. This allowed them to follow each cell as it moved to different parts of the heart. They also measured gene activity in individual cells and found that they showed distinct gene activity very early on, causing them to be allocated to different anatomical structures of the forming heart.
The fact that each heart cell population is distinguished so early on, may mean each group of cells is sensitive to specific environmental or genetic changes, which could explain why some conditions affect certain parts of the heart.
'Our finding that different parts of the heart arise in different locations may help researchers build better models using stem cells,' said Dr Kenzo Ivanovitch, who is the lead author of the study. 'We can now envisage generating cells pre-determined to become specific parts of the heart and could use these to model disease or develop and test new regenerative therapies.'