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Ph.D., The City University of New York
Neural crest cells, are a stem cell population that migrates from the neural tube early in development. They migrate extensively throughout the embryo and form most of the head and peripheral nervous system, giving rise to sensory and sympathetic ganglia, heart regions, glia, head bones, teeth, muscle cells, sensory organs, melanocytes and other cell types.
The neural crest is interesting because of its unique origin, development and differentiation. These cells are initially part of the dorsal neural tube, with a clear epithelial character; later, they transform into actively motile mesenchymal cells. All these changes are very similar to the one that occurs during CANCER metastasis. Thus, neural crest stem cells make an excellent model cell to study metastasis, migration and cell fate determination in a stem cell population.
The lab projects are:
1) Understand neural crest migration as modulated by the Tumor-suppressor Slit.
Neural crest cells are a multipotent cell lineage that delaminates from the dorsal neural tube of developing vertebrate embryos and subsequently undergo an epithelial to mesenchymal transition enabling stationary cells to actively migrate to distant areas. Neural crest EMT is valuable to study since the same process occurs in cancer metastasis. Mechanisms controlling migration of neural crest cells are not fully understood. Slit2 is a chemorepellant guidance molecule that stimulates the motility of trunk neural crest cells and repels them from the developing gut. Recently published research has identified Slit2 as a tumor suppressor molecule. The individual connections of neural crest cell EMT and Slit2 in cancer metastasis led us to believe that there may be a link between Slit expression and proper neural crest cell migration.
2) Identify molecules that determine the specific migratory pathways decisions by neural crest cells.
The neural crest is a migratory population of cells that gives rise to a wide range of cell types in the peripheral nervous system of vertebrate embryos. It has been shown that neural crest cells migrate along specific pathways throughout the embryo. The reason for such specificity is not fully known, although recent studies have described axon pathfinding repellants (ephrinB2, SemaIIIa, Slit2, etc.) to also be chemorepellents of neural crest cells. The goal of this study was to find which other molecules are capable of guiding the neural crest and their close derivatives, Schwann cell precursor cells (SCPC’s). Only certain neurotrophins were tested whose presence in the embryo spatiotemporally matches the migrating neural crest. Experiments by live imaging of cells exposed to a linear chemical gradient, and other methods suggest that: a) neural crest cells and SCPC’s are attracted to glial cell line-derived neurotrophic factor (GDNF), macrophage migration inhibitory factor (MIF), and Heregulinβ1; b) neural crest cell migration is stimulated in the presence of GDNF, Heregulinβ1, and nerve growth factor (NGF). These preliminary data suggest that neural crest cells and SCPC’s use a variety of neurotrophic factors as guiding cues during their extensive migration in the embryo.
3) Look at neural crest markers through evolution in sharks, snakes and lampreys.
The neural crest is responsible for the formation of the peripheral nervous system and head structures. We are looking into the evolution of neural crest in elasmobranches and other non-mammalian organisms by looking at the pattern of expression of genes like Sox10, Seraf, Sox2, etc during early development.
Walheim, C. Zanin, J.P. and de Bellard, ME. (2011). Analysis of trunk neural crest cell migration using a modified Zigmond chamber assay. Journal of Visual Experiments. Accepted.
Cornejo, M., Nambi, D., Walheim, C., Somerville, M., Walker, J., Kim, L., Ollison, L., Diamante, G., Vyawahare, S. and de Bellard, ME (2010). Effect of Neurotrophins in the Migration of a Schwann cell Precursor Line. Neurochemical Research. 35(10):1643-1651.
Reyes, M., .Zandberg, K., Desmawati, I. and de Bellard, ME (2010). The neural crest of snake embryos. BMC Developmental biology. 10:52.
El-Ghali, N., Rabadi, M., Ezin, M. and de Bellard, ME (2010) New Methods for Chicken Embryo Manipulations. Microscopy Research and Techniques73: 58-66.
Rotenstein, L., Milanes, A., Juarez, M., Reyes, M. and de Bellard, ME. (2009). Embryonic Development of Glial Cells and Myelin in the Shark Embryo Chiloscyllium punctatum. Gene Expression Patterns. 9: 572-585.
Rotenstein, L., Herath, K., Gould, RM. and de Bellard, ME. (2008). Characterization of the Shark Myelin Po Protein. Brain, Behavior & Evolution 72:48-58. [PMID: 18635929].
de Bellard, ME, Barembaum, M., Arman, O. and Bronner-Fraser, M. (2007). Lunatic fringe causes expansion and increased neurogenesis of neural tube and trunk neural crest populations. Neuron Glia Biology 3:1-11.