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Molecular Biology Program
 

Kristin Artinger, Assistant Professor

Ph.D. (1995), University of California - Irvine


 

 

 

 

Contact Info:

Molecular Biology
University of Colorado

Kristin Artinger, Ph.D.  Research One South
(RC1-South), Room 11112
Kristin.Artinger@ucdenver.edu Phone: 303-724-4562

 

 
 
     
    Research in my laboratory is directed towards an understanding of the molecular and genetic mechanisms involved in the development of the neural crest. Neural crest cells are born at the neural plate border, and have the extraordinary ability to retain stem cell-like characteristics. Once specified, they migrate through the embryo and give rise to a diverse array of derivatives, including peripheral neurons and glia, pigment cells and craniofacial cartilage, which form most of the vertebrate face. Thus, the neural crest is an attractive model system to study the gene regulatory networks involved in cell fate determination. Our work has focused on these specific questions:
     
    1. What are the genetic hierarchies involved in the specification and differentiation of neural crest cells?  Here, we are focusing on the transcriptional regulation of these processes, focusing on the zinc finger transcription factor Prdm1. When prdm1a is mutated in zebrafish, neural crest and Rohon-Beard sensory neurons are reduced, and the neural plate domain is expanded. Thus, Prdm1 controls the cell fate decision between neural crest cells and other cells at the neural plate border by both transcriptionally repressing and activating transcriptional targets. In the craniofacial region, prdm1a and other Prdm proteins play important roles in cell proliferation and aspects of craniofacial development respectively. Currently, we are determining how Prdm1 interacts with other transcriptional regulators and signals to pattern the vertebrate face.
     
    2. How do neural crest cells migrate along the correct migratory pathway?   Transcriptional profiling suggests that many of the genes regulated by neural plate border transcription factors are involved in cell migration. We are testing the hypothesis that neural plate border transcription factors regulate the processes of neural crest cell migration including genes such as chemokine signaling, cell-cell adhesion and cell-matrix adhesion genes. One such factor, cxcr4a, is expressed on cranial neural crest cells and sdf1b is expressed in the target tissue. Loss of cxcr4a causes neural crest migration and craniofacial cartilage and ganglia condensation defects.  Current work is focused on understanding the molecular mechanisms as well as identifying several other downstream targets involved in this process.
     
    In addition to these two main questions, we are preforming various types of screens (ENU mutagenesis, Morpholino, RNA-seq and miR-seq, ChIP-Seq) to identify novel factors controlling neural crest cells specification, migration and differentiation.  These have identified several factors important for these processes.  We currently use two main vertebrate species:  The zebrafish and the mouse. The zebrafish offer a unique model to study early vertebrate development since the embryos are transparent and allow us to follow cells in real time. In taking advantage of multiple developmental systems, we hope to utilize each model for its strengths to gain insight into the conserved molecular mechanisms required for neural crest cell development. Ultimately, we hope to generate an understanding of the process of neural crest development that will inform the repair and treatment of neural crest associated birth defects, such as cleft-lip and palate and other craniofacial syndromes, as well as cancer cell migration.
     
    Unique Techniques:
            • Mutagenesis screens in zebrafish
            • Molecular and genomic analysis
            • Embryological techniques such as microinjection and transplantation
            • In situ hybridization and immunohistochemistry
            • Live cell imaging

 

 

 

 

 

 

 

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.