My lab studies how the vertebrate embryo comes to be appropriately patterned along the anteroposterior (AP) axis. We use a combination of molecular, cellular and embryological approaches to address how specific regions of the body are patterned. In particular this includes studies of segmentation and regionalization, and the genes involved in these processes. We make use of the teleost zebrafish (Danio rerio) as a model system for these studies, because this species offers a number of unique advantages to the developmental biologist: the embryos are accessible from the earliest stages, they have complete optical clarity rendering them useful for cell lineage analysis and cell transplantation studies, and the zebrafish is also a good genetic system with many mutant lines available.

 We are particularly interested in the Hox genes. These are a family of genes which encode transcription factors implicated in regionalization of the embryo. They have a clustered genomic organization and have been highly conserved through evolution. Cephalochordates have a single cluster of Hox genes and tetrapod vertebrates have 4 such clusters (HoxA-D) that are believed to have arisen via a series of duplication and divergence events. Our recent work has revealed that the zebrafish have 7 clusters (Aa, Ab, Ba, Bb, Ca, Cb and Da), most likely as a result of duplications of all 4 chromosomes carrying Hox gene clusters, followed by loss of one of the clusters. We are interested in investigating when in the teleost lineage these duplications occurred by taking a comparative approach.

 We are also investigating Hox gene function, especially in the context of patterning of the hindbrain and cranial neural crest. The hindbrain is transiently segmented into a series of bulges termed the rhombomeres. This segmental organization correlates with domains of gene expression, lineage restriction, and neuronal organization, and serves to coordinate the migration of cranial neural crest into the adjacent branchial arches. The cranial neural crest gives rise to the skeletogenic components of the branchial arches and also plays a vital role in patterning the surrounding musculature. Thus the rhombomeric organization of the hindbrain plays a central role in patterning of the entire cranio-facial region. Individual Hox genes are expressed in distinct rhombomeres and branchial arches; null mouse mutants of these genes have revealed important patterning roles in these regions. We are now analyzing Hox gene function by taking a mis-expression approach and we are also studying mutant zebrafish with defects in hindbrain segmentation and branchial arch patterning.

McClintock, J. M., Kheirbek, M. A. and Prince, V. E. (2002). "Knockdown of duplicated zebrafish hoxb1 genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention." Development 129: 2339-54. PubMed Citation

Stafford, D. and Prince, V. E. (2002). "Retinoic acid signaling is required for a critical early step in zebrafish pancreatic development." Curr Biol 12: 1215-20. PubMed Citation

Hunter, M. P. and Prince, V. E. (2002). "Zebrafish hox paralogue group 2 genes function redundantly as selector genes to pattern the second pharyngeal arch." Dev Biol 247: 367-89. PubMed Citation

Moens, C. B. and Prince, V. E. (2002). "Constructing the hindbrain: insights from the zebrafish." Dev Dyn 224: 1-17. PubMed Citation

Prince, V. (2002). "The Hox Paradox: More complex(es) than imagined." Dev Biol 249: 1-15. PubMed Citation

Prince, V.E, Joly, L., Ekker, M. and Ho, R.K. (1997). Zebrafish hox genes: Genomic organization and modified colinear expression patterns in the trunk. Development, 125: 407-420.

 Prince, V.E. (1997). Hox genes and segmental patterning of the vertebrate hindbrain. American Zoology (in press).

 Prince V.E., Moens, C.B., Kimmel, C.B. and Ho, R.K. (1997). Zebrafish hox genes: Expression in wild-types and mutants for the segmentation gene, valentino. Development, 125: 393-406.

 Gale, E., Prince, V., Lumsden, A., Clarke, J., Holder, N. and Maden, M. (1996). Late effects of retinoic acid on neural crest and aspects of rhombomere identity. Development, 122: 783-793.

 Prince, V. and Lumsden, A. (1994). Hoxa-2 expression in normal and transposed rhombomeres: Independent regulation in the neural tube and neural crest. Development, 120: 911-923.

 Guthrie, S., Prince, V. and Lumsden A. (1993). Selective dispersal of rhombomere cells in orthotopic and heterotopic grafting experiments. Development, 118: 527-538.