Wellcome Early Career Award Fellow The Francis Crick Institute London, United Kingdom
Abstract: Fetal growth restriction (FGR) associates with long-term white matter disruption and neurological disabilities but the underlying mechanisms are unclear. Here, we establish mouse FGR models of maternal malnutrition and placental insufficiency that have largely normal neurogenesis but long-term adult undermyelination. We find that the adulthood forebrain myelin deficit is not associated with reduced number of myelin-making cells - oligodendrocyte precursor cells (OPCs) and their progeny, the oligodendrocytes themselves. Instead, FGR triggers a post-mitotic defect in oligodendrocyte growth and myelination. Surprisingly, this defect can be recapitulated with in vitro cultures of newly-formed OPCs from FGR mouse neonates, indicating that it is cell-intrinsic. Our findings together demonstrate that the life-long myelination potential of OPCs is strongly influenced by the exposure to environmental stressors during early development. They also open up a new avenue of mechanistic research into the neurological aspects of the non-genetic developmental origins of health and disease (DOHaD).
Funding Source: The project is funded by a Wellcome Early Career Award (Wellcome Trust) awarded to KHT Mau.
