Once an egg is fertilized, that single cell must divide repeatedly to become the myriad cell types that are properly positioned in a complex, multicellular organism. One way that cells arrange themselves in the developing embryo is by moving. The vertebrate neural crest is a striking example of developmental cell migration. Neural crest cells arise in the future brain and spinal cord, but become disconnected from their neighbors and migrate over long distances throughout the embryo to form surprisingly diverse derivatives, including the peripheral nervous system, outflow tract of the heart, and craniofacial skeleton. The importance of these events is clear: abnormalities in neural crest development lead to a variety of common birth defects (such as cleft lip/palate) and cancers (such as melanoma and neuroblastoma). Moreover, neural crest cell migration resembles cancer metastasis. To make sense of how things go wrong, we must first understand normal neural crest development. How do neural crest cells become different from their neighbors and migrate? How do they know where to go? How do they maintain their stem cell-like ability to give rise to so many different cell types? The Gammill lab uses chick and mouse embryos to elucidate the molecular mechanisms regulating neural crest formation, migration, and guidance. Building on a gene expression profile of a newly induced neural crest cell, our work has implicated several novel regulators of neural crest development. These include an antiphosphatase, a methyltransferase, and a tetraspanin that all affect neural crest development post-translationally. Our next task is to define the proteins modulated by these regulators. To achieve this we are combining embryological (explants, primary neural crest cell cultures) and molecular manipulations (electroporation of gain and loss of function reagents) of chick embryonic development with genomic analysis (ChIPseq and RNAseq) and proteomics (arrays, metabolic labelling, mass spectrometry), while relying on mouse mutants for robust genetic functional analyses. This combination of organisms and techniques allows us to integrate the advantages of each system toward a clearer understanding of early neural crest development.
Fairchild, C.A., Conway, J.A., Schiffmacher, A., Taneyhill, L.A. and Gammill, L.S. (2014) FoxD3 regulates cranial neural crest EMT via downregulation of Tetraspanin18 independent of its functions during neural crest formation. Mech. Dev. 132:1-12.
Vermillion, K.A., Lidberg, K.A. and Gammill, L.S. (2014) Expression of actin binding proteins and requirement for actin depolymerizing factor in chick neural crest cells. Dev. Dyn. 243(5):730-8.
Vermillion, K.A., Lidberg, K.A. and Gammill, L.S. (2014) Cytoplasmic protein methylation regulates neural crest migration. J. Cell Biol. 204:95-109.Jacques-Fricke B.T. and Gammill L.S. (2014) Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity. Mol Biol Cell 25:4174-86.
Fairchild, C.A. and Gammill, L.S. (2013). Tetraspanin18 is a FoxD3-responsive antagonist of cranial neural crest epithelial to mesenchymal transition that maintains Cadherin6B protein. J. Cell Sci. 126:1464-76.
Jacques-Fricke, B.T., Roffers-Agarwal, J. and Gammill, L.S. (2012). DNA methyltransferase 3b is dispensable for mouse neural crest development. PLOS One 7(10):e47794.
Roffers-Agarwal, J., Hutt, K.J. and Gammill, L.S. (2012). Paladin is an antiphosphatase that regulates neural crest cell formation and migration. Dev. Biol. 371(2):180-90.
Kulesa PM, Gammill LS. (2010) Neural crest migration: patterns, phases and signals. Dev Biol. 344(2):566-8.