The neural crest provides a unique population of migratory stem cells with which to study a variety of cell and neural developmental processes. Neural crest cells emerge from the neuroepithelium in development and transform into a mesenchymal/migratory population. Several inhibitory molecules have been shown to play important roles in neural crest migration including the chemorepulsive molecules Slit 1-3. Slit molecules were initially discovered as axonal guidance molecules;however, recently they have been also shown to be true tumor suppressors and affect cell proliferation in cancer cells. Neural crest cell migration has been repeatedly likened to the process of cancer metastasis and cell invasion. Slit molecules attenuate cancer progression by regulating beta-catenin expression and are also able to negatively regulate metastasis. Results from our previous grant demonstrated that Slit chemorepellant molecules impair neural crest cell migration and alters neural crest cells cytoskeletal organization towards a non- migratory phenotype. However, we still do not know the precise role that Slit molecules play on pre-migratory neural crest cells. Do Slit molecules prevent neural crest delamination in a manner analogous to the way Slits prevent tumor metastasis? If so, what are the molecular mechanisms that allow Slit molecules to prevent the delamination of the pre-migratory neural crest cells? Do Slits modulate pre-migratory neural crest cell proliferation? The significance of this proposal is that it will determne whether or not Slits have an effect on neural crest delamination during the epithelial-to- mesenchymal transition (EMT) via their """"""""tumor suppressor mechanisms"""""""" and/or if Slits modulate pre-migratory neural crest proliferation. The approach of this new proposal is to study of the role of Slit molecules in the pre-migratory neural crest cell using cell biology and genomic methods. The findings from this project will: 1) expand the current knowledge on the role of the tumor suppressor Slits in neural crest cell proliferation;2) determine if pre-migratory neural crest cels need to silence Slits before delamination;and, 3) provide insight into tumor suppressor activity by elucidating the role of Slits in cell migration.
The outcomes from this research will help us understand how we may be able to harness the metastatic aggressiveness of crest derived-cancers because it will look into the role that a tumor suppressor molecule, Slit, have on its progenitor population and correlate it with cancer aggressiveness.
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| De Bellard, Maria Elena; Ortega, Blanca; Sao, Sothy et al. (2018) Neuregulin-1 is a chemoattractant and chemokinetic molecule for trunk neural crest cells. Dev Dyn 247:888-902 |
| de Bellard, Maria Elena (2016) Myelin in cartilaginous fish. Brain Res 1641:34-42 |
| Giovannone, Dion; Ortega, Blanca; Reyes, Michelle et al. (2015) Chicken trunk neural crest migration visualized with HNK1. Acta Histochem 117:255-66 |
| Zuhdi, Nora; Ortega, Blanca; Giovannone, Dion et al. (2015) Slit molecules prevent entrance of trunk neural crest cells in developing gut. Int J Dev Neurosci 41:8-16 |
| Juarez, Marilyn; Reyes, Michelle; Coleman, Tiffany et al. (2013) Characterization of the trunk neural crest in the bamboo shark, Chiloscyllium punctatum. J Comp Neurol 521:3303-20 |
| Walheim, Christopher C; Zanin, Juan Pablo; de Bellard, Maria Elena (2012) Analysis of trunk neural crest cell migration using a modified Zigmond chamber assay. J Vis Exp : |
| Giovannone, Dion; Reyes, Michelle; Reyes, Rachel et al. (2012) Slits affect the timely migration of neural crest cells via Robo receptor. Dev Dyn 241:1274-88 |
| Reyes, Michelle; Zandberg, Katrina; Desmawati, Iska et al. (2010) Emergence and migration of trunk neural crest cells in a snake, the California Kingsnake (Lampropeltis getula californiae). BMC Dev Biol 10:52 |
| Cornejo, Martha; Nambi, Deborah; Walheim, Christopher et al. (2010) Effect of NRG1, GDNF, EGF and NGF in the migration of a Schwann cell precursor line. Neurochem Res 35:1643-51 |
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