Relevance to Pediatric Health
We are interested in how cells in developing embryos regulate their gene expression, signal to each other, and migrate during development. We have recently investigated how cellular metabolism impacts these processes.
Although C. elegans worms are clearly very different from humans, we have a lot in common. Worms have many of the same cell types we do including neurons, muscle, skin, and intestine. Due to evolutionary conservation, many of these cells express the same genes as human neurons etc. and the same genes are involved in specifying these cell types in developing embryos. Furthermore, metabolism has also been deeply conserved by evolution, so many of the genes that cause inborn errors of metabolism and other metabolic diseases in humans also disrupt the health of C. elegans.
Like humans, C. elegans also depends on its diet as a source of vitamin B12, a critical micronutrient that impacts cellular metabolism. Humans must get vitamin B12 from animal food sources, since plants do not produce this vitamin, so vegans and vegetarians are at high risk for deficiency, as are patients taking common drugs like antacids and metformin. Maternal deficiency in vitamin B12 or defects in its processing can result in structural birth defects including spina bifida, heart defects, and omphalocele as well as low birth weight, preterm birth and miscarriage (Refs: https://pubmed.ncbi.nlm.nih.gov/22116453/ and https://pubmed.ncbi.nlm.nih.gov/35818085/). The standard laboratory diet for C. elegans is actually low in vitamin B12 and we found that supplementing mothers with vitamin B12 could actually increase the survival rate of mutant embryos prone to a structural birth defect in tissue fusion from 40% to 63%. Vitamin B12 serves as a critical enzymatic co-factor in two different metabolic pathways in both humans and worms. It is needed to breakdown propionic acid in mitochondria, which removes a toxic byproduct and also generates additional energy, and to generate methyl donors for protein and DNA methylation, which are critical for regulating chromatin in the process of cell differentiation. We found the ability of vitamin B12 to rescue the structural defect is due to its function in mitochondria, and that antioxidants or additional sources of energy can partially rescue.
