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School of Dental Medicine Faculty

KRISTIN BRUK ARTINGER Assistant Professor Craniofacial Biology Mail Stop 8120, RC1-S, Rm L18 11112 12801 E. 17th Ave Aurora, CO 80045 Phone: 303-724-4562 Fax: 303-724-4580 Email: Kristin.Artinger@uchsc.edu

Education:    
Ph.D. University of California – Irvine

Postdoctoral Training:
Massachusetts General Hospital/Harvard Medical School
Cell Biology, Harvard Medical School

Research Interests: 

Early Spinal Cord Development
Research in my lab is directed toward an understanding of the molecular, genetic and developmental mechanisms involved in the patterning of the early spinal cord (neural plate) during vertebrate embryogenesis. There are several different populations of cells at the lateral border of the neural plate: Neural crest cells, Rohon-Beard sensory neurons, and placodal cells. One of these cell populations, namely neural crest cells, have the extraordinary ability to retain stem cell characteristics during development and give rise to multiple derivatives, including peripheral neurons, pigment cells and craniofacial cartilage. 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 novel genes involved in the specification of neural crest cells and Rohon-Beard sensory by doing genetic screens in zebrafish.
2. How do the novel and existing genes that are involved in the specification of these cells fit into the molecular cascade? What is the role of specific transcription factors in this process?
3. What are the lineal relationships between cell types at the neural plate border? Do they require the same set of inductive cues? What are the molecular signals that induce them?

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. We have completed a zebrafish genetic screen for mutants that affect neural crest cell and sensory neuron development at the border of the neural plate (Artinger et al, 1999 ). One of the mutations found in the screen, narrowminded (nrd), is a cell autonomous mutation that affects specification of neural crest and Rohon-Beard sensory neurons at border of the neural plate. Both cell types are absent or reduced in nrd. We have identified the gene that is defective in the nrd mutation as prdm1, a SET/zinc finger transcription factor (Hernandez-Lagunas, et al 2005). The analysis of prdm1 function will likely uncover novel mechanisms in the specification of cells at the neural plate border. Further, we have recently shown that a homeobox transcription factor, Dlx3, is involved in the specification of cells at the border of the neural plate. 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 pattern of the neural plate border. Ultimately, we hope to combine molecular genetic approaches in zebrafish with experimental approaches in Xenopus to generate an understanding of the process of spinal cord development and regeneration in vertebrates.

Unique Techniques:

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

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.

Belting HG, Hauptmann G, Meyer D, Abdelilah-Seyfried S, Chitnis A, Eschbach C, Soll I, Thisse C, Thisse B, Artinger KB, Lunde K, Driever W. spiel ohne grenzen/pou2 is required during establishment of the zebrafish midbrain-hindbrain boundary organizer. Development. 2001 Nov;128(21):4165-76.

Kim CH, Oda T, Itoh M, Jiang D, Artinger KB, Chandrasekharappa SC, Driever W, Chitnis AB. Repressor activity of Headless/Tcf3 is essential for vertebrate head formation. Nature. 2000 Oct 19;407(6806):913-6.

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.


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