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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 development of 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 specification and differentiation. The work has focused on these specific areas:
Selected Publications
Hernandez-Lagunas L, Choi IF, Kaji T, Simpson P, Hershey C, Zhou Y, Zon L, Mercola M, Artinger KB. Zebrafish narrowminded disrupts the transcription factor prdm1 and is required for neural crest and sensory neuron specification. Dev Biol 2005 Feb 15;278(2):347-57. Kaji T, Artinger KB. dlx3b and dlx4b function in the development of Rohon-Beard sensory neurons and trigemnal placode in the zebrafish neurula. Dev Biol 2004 Dec 15; 276(20): 523-40. Zhang C, Basta T, Hernandez-Lagunas L, Simpson P, Stemple DL, Artinger KB, Klymkowsky MW. Repression of nodal expression by maternal B1-type SOXs regulates germ layer formation in Xenopus and zebrafish. Dev Biol 2004 Sep1;273(1):23-37. Woda JM, Pastagia J, Mercola M, Artinger KB. Dlx proteins position the neural plate border and determine adjacent cell fates. Development 2003 Jan;130(2):331-42. Artinger KB, Chitnis AB, Mercola M, Driever W. Zebrafish narrowminded suggests a genetic link between formation of neural crest and primary sensory neurons. Development. 1999 Sep;126(18):3969-79. |
Faculty
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Web Design by Craig Kelly Graphic Design |
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To answer these questions, we primarily use the zebrafish model in addition to the frog, Xenopus lavis and the mouse. To identity the molecular mechanisms involved in specifying these cells, we have focused on the role of transcription factors in this process. We have recently determined that a zinc finger transcription factor, prdm1a, is required for the specification of neural crest cells and Rohon-Beard sensory neurons. Once neural crest cells are specified, they then migrate out of the CNS and differentiate into specific derivatives, including craniofacial cartilage. We have uncovered a role for chemokine signaling in neural crest migration as well an additional role for prdm1a in the differentiation of craniofacial structures. Embryos that have a loss of prdm1a function have a severe reduction in posterior craniofacial structures suggesting a later role of prdm1a in differentiation of neural crest cells in the branchial arches. In taking advantage of the both the multiple developmental systems, we hope to gain insight into the molecular mechanisms responsible determination of neural crest cell pattern early at the neural plate border and later in the craniofacial development. Ultimately, we hope to combine molecular genetic with experimental approaches 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.