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Early Neural Crest Development Research in my lab is directed toward an understanding of the molecular, genetic and developmental mechanisms involved in the patterning of the early neural crest during vertebrate embryogenesis. There are several different populations of cells at the lateral border of the neural plate in addition to neural crest cells including Rohon-Beard sensory neurons and placodal cells. One of these cell populations, namely neural crest cells, have the extraordinary ability to retain stem cell-like characteristics during development and give rise to multiple derivatives, including peripheral neurons, pigment cells and craniofacial cartilage, which makes up most of the vertebrate face. This combination has made it an attractive model system to study cell fate determination. The work has focused on these specific areas:

1. Identification of genetic hierarchies involved in the specification and differentiation of neural crest cells.
2. Understanding the developmental relationships and inductive mechanism of neural crest and Rohon-Beard sensory neurons.
3. Identification of the developmental potential and molecular mechanisms of neural plate border progenitor cells to maintain a stem cell-like fate.

To answer these questions, we use two main vertebrate species: The zebrafish and the frog, Xenopus lavis. Zebrafish is an ideal system to study vertebrate development since the embryos have a quick generation time, are transparent and have the ability to do genetics. Xenopus are ideal for embryological manipulations, due to their large size and ease of manipulation. A zebrafish genetic screen identified a mutation in prdm1 (narrowminded), a SET/zinc finger transcription factor (Artinger et al, 1999; Hernandez-Lagunas, et al 2005) The specification of neural crest and Rohon-Beard sensory neurons at border of the neural plate are defective in prdm1 mutants: Both cell types are absent or reduced. In addition, a severe reduction in posterior craniofacial structures is also observed, suggesting a later role of prdm1 in differentiation of neural crest cells in the branchial arches. The analysis of prdm1 function will likely uncover novel mechanisms in the specification of cells at the neural plate border and differentiation of cells in the branchial arch. In taking advantage of the both the zebrafish and Xenopus system, we hope to gain insight into the molecular mechanisms responsible for setting up the neural crest pattern early at the neural plate border and later in the branchial arches. Ultimately, we hope to combine molecular genetic approaches in zebrafish with experimental approaches in Xenopus to generate an understanding of the process of neural crest development and regeneration in vertebrates. The mechanisms identified in these studies will likely yield important information for the prevention and repair of neural crest associated birth defects, such as cleft-lip and palate.

Unique Techniques:

• mutagenesis screens in zebrafish
• molecular and genomic analysis
• embryological techniques such as microinjection and transplantation
• in situ hybridization and immunohistochemistry