INVESTIGATOR: Larissa Patterson, Rhode Island College
MENTOR: Eleana Oancea, Brown University
THEME: Cancer

ABSTRACT: Melanoma is by far the deadliest form of skin cancer since it is the most like to metastasize and spread to other regions of the body. Once melanoma begins to spread, the prognosis is poor. Melanocytes, the cells that are transformed in melanoma, are derived from the embryonic neural crest. Neural crest is a transient population of embryonic cells that also gives rise to craniofacial bone and cartilage, peripheral nerves and glia and other cells types. Neural crest cells undergo an epithelial to mesenchymal transition (EMT) to detach from their origin in the dorsal neural tube, invade underlying tissues and migrate vast distances to their final positions throughout the embryo. Embryonic neural crest cells are highly proliferative, multipotent and migratory, and tumors derived from transformations of neural crest derivates are particularly difficult to treat. Identifying the mechanisms that suppress migratory behaviors and promote the acquisition of stable cellular phenotypes during embryonic development could prove invaluable for developing new treatment options for malignant melanomas. In particular, the identification of genes that halt migration and maintain melanocytes in their final positions within the larval stripes could provide important therapeutic targets to slow or stop melanoma metastasis. The zebrafish early larval pigment pattern is a tractable system for studying the cellular behaviors and molecular signals that regulate melanocyte migration and differentiation. Aim 1 of this study will examine the roles of homeobox transcription factors alx4a and alx4b in repressing migratory behavior and promoting terminal differentiation of embryonic neural crest cells. Aim 2 of this study will elucidate mechanisms that guide migrating melanocyte precursors to their final locations and promote the survival and maintenance of melanocytes in the larval stripes. Together these proposed studies will provide insight into the ontogenetic mechanisms that promote melanocyte migration from the neural crest to their final embryonic locations and could provide important therapeutic targets to slow melanoma metastasis through the identification of molecular signals that halt migration and maintain melanocytes in stripes. This research is well suited for undergraduates and will allow Rhode Island College students to gain first-hand experience with modern developmental biology techniques and experimental approaches.

RELEVANCE: Melanoma is an aggressive form of skin cancer that develops from melanocyte pigment cells. During initial stages of melanoma metastasis, cells reactivate portions of the embryonic melanocyte program to increase plasticity and facilitate migration. Identifying the mechanisms that promote embryonic melanocyte differentiation and migratory arrest could prove invaluable for developing new treatments to stop or slow tumor progression.