Investigating lipid droplet regulation and function in the developing neural tube

The National Institute of Child Health and Human Development awarded The Regents of the University of Colorado $430,375 on August 27, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to investigate lipid droplet regulation and function in the developing neural tube.

The research addresses how embryonic neural tubes utilize lipids to control development and how maternal metabolic disorders—type 2 diabetes and obesity—increase the risk of neural tube defects including anencephaly and spina bifida. The project examines lipid droplet dynamics during neural tube closure, an understudied morphogenetic process, and investigates how lipid abnormalities in maternal metabolic disorders contribute to structural birth defects. The work encompasses lipid uptake, synthesis, storage in lipid droplets, and lipid droplet breakdown to understand critical cellular processes during embryonic development.

The award is a Project Grant with a period of performance extending through July 31, 2028. Place of performance is Boulder, Colorado. The Regents of the University of Colorado, operating through its Office of Contracts and Grants Division, is the recipient.

Abstract

The prevalence of lipid abnormalities and metabolic syndromes has increased significantly in recent years in the united states. These metabolic disorders affect not only the adult living with them but can also adversely affect the embryo and fetus during pregnancy. Maternal type two diabetes and obesity are associated with an increased risk for structural birth defects in the child. These include neural tube defects such as anencephaly and spina bifida, which disrupt formation of the embryonic brain or spinal cord and result in life-long health complications or death. Lipids are critical throughout our bodies for energy, cell signaling, and building blocks for membranes that surround our cells and organelles. However, IT is unknown how the embryonic neural tube utilizes lipids to control its development or how non-genetic factors like diabetes and obesity contribute to an increased risk for neural tube defects. Lipid metabolism encompasses a balance between lipid uptake or synthesis, storage in lipid droplets to ensure lipids do not build up to toxic levels, and lipid droplet breakdown to supply enough lipids to mediate necessary cellular processes. There is good understanding of the basic biology and pathobiology of lipid metabolism, however there is a GAP in the field of how lipid droplets are regulated during critical embryonic processes and the consequences of lipid abnormalities on embryonic development. In oocytes and up to preimplantation development, IT has been shown there are dynamic changes in lipid droplets and that the lipid pool is needed to regulate oocyte quality, cell proliferation, and lumen formation. Lipid metabolism and function is vastly understudied during the dynamic morphogenetic process of neural tube closure. EM studies in 1992 and our preliminary data show a dynamic change in lipid droplet number, size, and cellular location as the flat neural plate bends up to form the closed neural tube. Our first aim is to generate a spatiotemporal atlas of lipid droplet dynamics during neural tube closure. We will study both mouse neural tube closure and human ipsc-derived neural tube-like organoids to determine common and differential behaviors of lipid droplets as cells apically constrict, proliferate, and guard against lipid toxicity. Our second aim is to begin a mechanistic dissection of the functions of lipid droplets during neural tube closure. We will manipulate lipid droplet formation or mobilization to define how this affects neural tube closure. We will also explore lipid droplet regulation in the neural tissue of embryos from diabetic pregnancies and the consequences of lipid dysregulation. The high and rising rates of lipid abnormalities and metabolic syndromes pose a serious burden to american health and are significant risk factors for structural birth defects in developing embryos. Our experiments will provide a framework for the study of lipid metabolism and functions in embryonic neural tube development. In turn, these results will provide new insight for the consideration of at- risk pregnancies.