Funding outcome

A newborn's first breath is driven by the rhythmic contraction of the diaphragm. But what happens if this essential muscle has not grown properly? In a condition called congenital diaphragmatic hernia (CDH), the diaphragm muscle grows with a hole in it, letting the intestines push up into the chest and crush the growing lungs. When a baby with CDH is born, it struggles to breathe because its lungs are damaged, and it needs urgent medical care. Unfortunately, in about 1 in 3 cases, newborns with CDH do not survive. Despite the severe impact that CDH has on newborns, we are still trying to understand its cause. We are particularly interested in understanding the importance of how the essential micronutrient vitamin A works during pregnancy to help the diaphragm and lungs grow, and how problems with this process might cause CDH. When thinking about how the growing lungs are damaged in CDH, we want to test the idea that problems with vitamin A function during pregnancy have direct and indirect effects on the lungs. We have recently shown that blocking how vitamin A works in the developing diaphragm causes CDH in mice. We want to study this mouse model and use it to better understand how the lung becomes damaged in CDH. First, we want to characterize the lung defects in this new model and compare it with lung defects seen in human CDH. Second, we want to grow these lungs in a test tube and determine the importance of vitamin A in the direct and indirect effects of CDH on the lungs. Third, we want to perform an in-depth analysis of every cell in the growing lungs from this mouse model and compare it to similar data from human CDH lungs. This research will help validate our mouse model of CDH and its relevance as a tool to study human CDH, it will also help us understand how important vitamin A is in CDH and its effect on the growing lungs. The better we understand the causes of lung damage in CDH, the better we will be prepared to prevent and treat it in the future.