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NIH grant 1R21HD123148-01: Investigating lipid droplet regulation and function in the developing neural tube
Institute: {'code': 'HD', 'abbreviation': 'NICHD', 'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development', 'admin_org_id': '12500030', 'admin_funding_url': ''}. PI: Lee A. Niswander. Award: $430375.
Start: 2026-08-27T00:00:00.
Summary
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.document fetched 2026-09-06 02:47