Robert Aaron Cornell
robert-cornell@uiowa.edu

Associate Professor

Training

BS Stanford University Biological Sciences, 1987
PhD University of Washington Biochemistry, 1995
Postdoc University of Oregon Neuroscience/Genetics, 1995-01

Current lab members:
Greg Bonde, Head Research Assistant, gregory-bonde@uiowa.edu

Wei Li, PhD candidate, Interdisciplinary Program in Genetics,
wei-li-4@uiowa.edu

Jaime Sabel, PhD candidate, Interdisciplinary Program in Genetics,
jaime-sabel@uiowa.edu

Matt McNeill, PhD candidate, Interdisciplinary Program in Neuroscience,
matthew-mcneill@uiowa.edu

Eric Van Otterloo, graduate student,
Department of Anatomy and Cell Biology
eric-vanotterloo@uiowa.edu

Research Interests/Laboratory Efforts

Many birth defects result from failure of the establishment or maintenance of cell fate. Which gene products direct multi-potent embryonic precursor cells to adopt specific fates? How do they do so, and with what other genes or gene products do they interact? By answering these questions we hope to improve the ability of clinicians to diagnose and treat developmental disorders. In addition, the genes that regulate embryonic development are likely to be the ones that regulate the differentiation of adult stem cells. The basic biology of stem cells needs to be better understood before their therapeutic potential can be realized. Finally, virtually all genes important in cancer are also developmental genes. Thus, an improved understanding of gene regulatory networks that operated during embryonic development could benefit multiple clinical fields.

We focus on neural crest, a population of embryonic precursor cells with the potential to adopt diverse fates, including pigment cells, sensory neurons, muscle, cartilage, and autonomic neurons. The broad developmental potential of neural crest makes it a good model for the embryo in general, and a variety of debilitating diseases affect neural crest derivatives. We focus on gene pathways that regulate establishment and maintenance (survival) of specific neural crest lineages, and of neural crest per se.

In these studies we use zebrafish, a vertebrate model system well
suited to genetic and embryological methods. We have projects
focussed on, a) understanding why disruption of ion channel TRPM7 causes melanocyte death and embryonic paralysis, b) the role of transcription factor AP-2 proteins in neural crest specification and survival, and c) the role of transcription factor Irf6 in normal craniofacial development.

Figure: Images of live wild type (left panels) and homozygous touchtone (right panels) mutant zebrafish. In touchtone mutant embryos, all embryonic melanocytes differentiate poorly and a fraction die, but residual melanocytes recover starting at day 3. Most homozygous mutants die by three weeks of age. Surviving homozygotes are severely reduced in body size, and display abnormal timing of calcification in endochondral and intramembranous bones. Adult melanocyte populations are normal. Meiotic mapping revealed touchtone corresponds to gene encoding divalent cation channel transient receptor potential Melastatin 7 (trpm7). See Cornell et al 2004 and Elizondo et al 2005.

Selected Publications

Cornell RA, Eisen JS. (2000) Delta signaling mediates segregation of neural crest and spinal sensory neurons from zebrafish lateral neural plate. Development . 127(13):2873-82.

Cornell RA, Eisen JS. (2002) Delta/Notch signaling promotes formation of zebrafish neural crest by repressing Neurogenin 1 function. Development 11:2639-48.

Cornell, R. A. , Yemm, E., Li , W. , D'Alencon, C., Wegman, L., Eisen, J. S., Zahs, A. (2004) Touchtone promotes survival of embryonic melanophores in zebrafish. Mechanisms of Development , 121(11): 1365-76.

O'Brien, E., d'Alencon, C., Schoenebeck, J., Murray, J., Allende, M., Gelb, B., Yelon, D., Eisen, J. S., and Cornell, R. A. (2004) Transcription factor Ap-2a is necessary for development of embryonic melanophores, autonomic neurons, and pharyngeal skeleton in zebrafish. Developmental Biology , 265 : 246-261.

Lee, L., Seftor, E. A., Bonde, G., Cornell, R. A., Hendrix M. J.C. (2005) The fate of human malignant melanoma cells transplanted into zebrafish embryos: Assessment of migration and cell division in the absence of tumor formation. Developmental Dynamics . 233:1560-70.

Cornell RA, Eisen JS. (2005) Notch in the pathway: the roles of Notch signaling in neural crest development. Semin Cell Dev Biol . 16:663-72. Review.

Elizondo , M. R., Arduini, B. L., Paulsen, J., Sabel, J. L., MacDonald, E. L., Henion, P. D.*, Cornell, R. A. * , Parichy, D. M.* (2005) Accelerated endochondral ossification and delayed intramembraneous ossification in dwarf zebrafish with mutations in trpm7 . Current Biology , 15: 667-671. *, corresponding authors.

McNeill, M., Bonde, G., and Cornell, R. A. (2007). Cell death of melanophores in zebrafish trpm7 mutant embryos depends on melanin synthesis. J Invest Dermatol . 127:2020-30

Li, W., and Cornell, R. A. (2007) Redundant activities of Tfap2a and Tfap2c are required for neural crest induction and development of other non-neural ectoderm derivatives in zebrafish embryos. Developmental Biology, 304:338-54.

Honors
1997-98 - NIH Postdoctoral Fellowship
1999 - NIH Postdoctoral Fellowship, Competitive Renewal
2001 - Recipient: Holden-Carver American Cancer Society Seed Grant
2002 - Recipient: Carver Medical Research Initiative Grant
2003 - Iowa Biological Sciences Funding Project
2005 - NIH RO1

National/International Committees

1997 - present Member, Society of Developmental Biologists.
2001 - present Member, AAAS
2004 - present Member, American Association of Anatomists
2005 - present Member, Panamerican Society for Pigment Cell Research
2005 - present Member, Society for Neuroscience