The goal of our research is to understand how diverse cellular behaviors, such as proliferation, migration, and differentiation, are regulated during embryonic development. Collective cell migration, which involves a cohort of cells moving together in a specific direction while maintaining cell-cell contacts, is required in the developing embryo during organ formation. In adults, collective cell migration is required for tissue homeostasis and wound healing. In addition, many invasive cancers have been shown to spread collective groups of cells. The precise molecular and cellular mechanisms that drive collective cell migration are not well understood. Understanding how cellular interactions are regulated in the context of developmental collective cell migration will shed light on how these processes are dysregulated in some invasive cancers.
Development of the zebrafish lateral line has proven to be an elegant model for studying collective cell migration, as it is amenable to live imaging and genetic manipulation. The lateral line is a mechanosensory system that allows aquatic vertebrates to sense changes in water current and regulates behaviors such as schooling and feeding. In the zebrafish, the posterior lateral line (pLL) forms from the posterior lateral line primordium (pLLP), a cohort of ~100 cells which collectively migrate along the trunk of the developing embryo. The pLLP is composed of proliferative progenitor cells and organized epithelial cells that will form the mechanosensory organs of the pLL. In the lab we have several mutant zebrafish lines that show distinct defects in the collective cell migration of the pLLP. Additionally, we are using CRISPR-Cas9 mediated genome-editing to generate targeted mutations to identify genes that disrupt collective cell migration. Defining the cellular and molecular hallmarks of collective cell migration is critical to finding treatments to correct defective cell migration during both development and disease.
Harding MJ, McGraw HF, Nechiporuk A. The roles and regulation of multicellular rosette structures during morphogenesis. (2014). Development (Cambridge, England), 141 (13), 2549-58. Journal Article, Review.
Malmquist SJ, Abramsson A, McGraw HF, Linbo TH, Raible DW. Modulation of dorsal root ganglion development by ErbB signaling and the scaffold protein Sorbs3. (2013). Development (Cambridge, England), 140 (19), 3986-96. Journal Article.
McGraw HF, Snelson CD, Prendergast A, Suli A, Raible DW. Postembryonic neuronal addition in zebrafish dorsal root ganglia is regulated by Notch signaling. (2012). Neural development, 7 23. Journal Article.
Prendergast A, Linbo TH, Swarts T, Ungos JM, McGraw HF, Krispin S, Weinstein BM, Raible DW. The metalloproteinase inhibitor Reck is essential for zebrafish DRG development. (2012). Development (Cambridge, England), 139 (6), 1141-52. Journal Article.
McGraw HF, Drerup CM, Culbertson MD, Linbo T, Raible DW, Nechiporuk AV. Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium. (2011). Development (Cambridge, England), 138 (18), 3921-30. Journal Article.
McGraw HF, Nechiporuk A, Raible DW. Zebrafish dorsal root ganglia neural precursor cells adopt a glial fate in the absence of neurogenin1. (2008). The Journal of neuroscience : the official journal of the Society for Neuroscience, 28 (47), 12558-69. Journal Article.
Loi PK, McGraw HF, Tublitz NJ. Peptide detection in single cells using a dot immunoblot assay. (1997). Peptides, 18 (5), 749-53. Journal Article.
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