The neural crest are cells that emerge shortly after neural tube closure and give rise to the wide variety of neuronal and non-neuronal derivatives that make a large number of head structures and the peripheral nervous system. These cells go from a non-motile, closely adherent cell type, to a highly motile one that allows them to migrate rapidly throughout the embryo and reach distant areas where they differentiate. In addition, neural crest cells encompass a stem cell- like population that can give rise to neurons, glia, melanocytes, facial bone, cornea, etc. The range of birth defects caused by neural crest cells misdirection or death goes from cleft palate (failure of the neural crest to close both sides of the face) to Hirschprung disease/Megacolon (failure of the neural crest to colonize the colon) to Neurofibromatosis (scattered small tumors of neural crest origin). Little is known about the underlying mechanism directing the process of neural crest migration. My preliminary data showed that Slit axonal chemorepellants are important in timing the entry into the gut of one population of neural crest versus another. The goal of the proposed study is to examine the mechanism by which Slit molecules, possibly through its putative Robo receptor repeal trunk, not vagal neural crest migration. Specifically, this project will: a) Examine the function of Robo receptors in repulsion of trunk neural crest migration in cells, b) Determine the role of Slit in preventing trunk, but not vagal neural crest from entering the gut. In summary, these experiments will contribute to our understanding of the multiple roles that Slit chemorepellants play in the formation of the gut by preventing trunk neural crest migration into its region and if the repulsive effects observed in trunk crest cells are Robo mediated. Narrative The goal of the proposed study is to examine the roles and interactions between Slit and Robo molecules have on vagal and trunk neural crest guidance and migration. Altogether preliminary data suggest that there is more to Slit molecules than being just a chemorepellant molecules, that they may be involved in other functions besides guidance. However, it is still not known why trunk neural crest cells will not enter the forming gut while vagal will. It is the aim of this proposal to investigate further this possibility by looking at Slit function in vagal and trunk crest migration of neural crest cells and in looking for Robo's role in this phenomenon. The significance of these experiments stems from its novel approach to study neural crest migration and the mechanism by which Slit molecules guide them during development. Very important, we still do not understand the mechanisms by which Slits have a dual function in both inhibiting and stimulating motility of trunk, not vagal neural crest cells. I propose to study these questions through a multi-faceted approach: embryological and cell biological/molecular. ? ?

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Academic Research Enhancement Awards (AREA) (R15)
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Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
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Morris, Jill A
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California State University Northridge
Schools of Arts and Sciences
United States
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Martinez, Darwin; Zuhdi, Nora; Reyes, Michelle et al. (2018) Screen for Slit/Robo signaling in trunk neural cells reveals new players. Gene Expr Patterns 28:22-33
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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