Mechanisms Underlying Vertebrate Wnt Gradient Formation: Wnt1 and Wnt3a are morphogens that control proliferation and cell fate specification in the developing chick spinal cord. As the dose of a morphogen controls the downstream responses of target cells, it is critically important to understand how Wnt gradients are formed. Although much is known about the downstream signaling pathways activated by Wnt proteins, little is known about the processing and secretion of Wnt proteins. We are currently investigating the biochemical, cellular and developmental roles of Porcupine and Wntless, two upstream regulators of Wnt secretion and gradient formation.
Development of a Biochemical Assay for Wnt Palmitoylation: The palmitoylation of Wnt proteins by Porcupine is critical for Wnt gradient formation. To better understand the biochemistry underlying this critical modification, we need to be able to easily measure Wnt palmitoylation. Unfortunately, the assays that are most often used to measure Wnt palmitoylation are cumbersome and slow. We are using a "click" chemistry based approach to develop an assay that will facilitate the study of Porcupine structure and function. This work is funded by an NSF RUI grant.
Investigating the Role of Porcupine in Neural Tube Closure: Defects in neural tube closure are amongst the most common birth defects. Wnt signaling pathways are known to be required for proper neural tube closure. Mutations in Porcupine cause a variety of defects in mouse and human, including possible defects in neural tube closure. We are performing experiments in the chick model system to more fully understand the role of Porcupine in neural tube closure. This work is funded by an NIH AREA grant.