The role of NSD3-mediated protein methylation in neural crest development

University Of Minnesota-Twin Cities, Minneapolis MN

Investigators

Abstract

Neural crest cells are migratory stem cells that break free from the developing brain and spinal cord during normal development in embryos with backbones. After they migrate, neural crest cells form numerous structures, including facial bones and cartilage, part of the heart, and neurons outside the brain and spinal cord. In order to migrate, neural crest cells make proteins that give them the ability to move and invade tissues. The longevity, location within a cell, and activity of these proteins are determined by chemical modifications. These protein modifications include the attachment of methyl groups by enzymes called methyltransferases in a process called methylation. This proposal aims to decipher the role of methylation in coordinating protein activity to achieve neural crest migration. Specifically, experiments will define the role of the methyltransferase NSD3 that preliminary data show is essential for neural crest migration. In this grant, molecular embryology and live cell imaging are used to characterize NSD3 to understand where it acts in neural crest cells and the migratory behaviors it controls. The data from these experiments will uncover basic mechanisms of neural crest migration that go awry in birth defects and are reactivated during cancer metastasis. This project has broader impacts by including undergraduates through post-doctoral fellows, women, and minorities in a diverse research team, with all members regularly sharing their work through publication, presentation at conferences, and outreach to the community.