Room: Z 316, Biological Sciences
Phone: (780) 492-4403
Fax: (780) 492-9234
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As neurons differentiate, they must acquire highly specialized regional identities. Their positional information is integrated into appropriate axon guidance, ensuring that the neuron connects to its desired target tissue. Our research group investigates the formation of the vertebrate central nervous system, with a focus on identifying cell to cell signaling mechanisms in the brainstem and eye. These projects utilize zebrafish as a model system, a vertebrate that is easily grown in large numbers, whose genome is largely sequenced, and for which robust gene manipulation tools permit the rapid creation of transgenics and knockdowns. Our research laboratory studies three diverse fields: (1) formation of the zebrafish eye with a goal of identifying genes that control the identities of retinal ganglion cells; (2) cell-cell signaling that regulates regional identity in the developing brainstem (hindbrain) with a goal of identifying models for human cranial dysinnervation disorders; and (3) broader studies on the genes involved in eye and brain formation, with a focus on leukemia-causing oncogenes.
1. Morphogenesis of the zebrafish eye (Curtis French, Timothy Erickson, Karyn Berry). The vertebrate eye is comprised of three main regions: anterior segment (tissues that regulate the amount of light received and maintain constant pressure within the eye); neural retina (photoreceptors and neurons to transmit light signals to brain); and the retinal pigmented epithelium (a tissue layer that supplies the photoreceptors with needed visual transduction molecules). The focus of our research is currently on the mechanisms that create regional identity for the retinal ganglion cells, a class of neurons that extend their axons, via the optic nerve, to the optic tectum. In particular, we are investigating BMP (bone morphogenetic protein) growth factor signaling in the retina and how it is regulated.
The brainstem is the region of your brain just above your spinal cord and contains a series of medically important neurons, known as the cranial nerves. If these nerves do not reach their appropriate targets, or die as a result of infection, a series of clinically important diseases result. These span from Duane retraction and Okihiro syndromes – affecting nerves that control muscles surrounding your eyes – to disorders such as Bell's palsy in which the facial nerves innervating your face are damaged as a result of viral infection. Our research on the brainstem has focused on cell-cell signaling that regulates neuron specification. In particular, we are studying retinoic acid, a derivative of vitamin A that regulates neuron identity. The cranial nerves are patterned by differing levels of retinoic acid, with higher concentrations in posterior regions and lower levels anteriorly. Our current research aims to identify the pathways that control retinoic acid levels. We are focusing on identifying genes that regulate enzymes that control retinoic acid synthesis and degradation and have made excellent progress recently at identifying factors in this pathway.
3. Studies of leukemia-causing oncongenes (Laura Reaume, Timothy Erickson).
Leukemia is caused by alteration in gene expression and function that affect a specific lineage of hematopoietic cells. Two of the molecules genes studied in brain and eye formation are implicated in the etiology of leukemia. For example, Pbx1 is the cause of approximately one quarter of all pediatric cases of pre-B cell acute lymphoblastic leukemia. A protein that binds Pbx, known as Meis, is also implicated in leukemia formation. Our research goal is twofold: (1) to build zebrafish models of leukemia that express human leukemic oncogenes in blood forming cells; and (2) to determine the endogenous function of Pbx, Meis, and Hox in blood formation.
We are currently recruiting Undergraduate Students (summer NSERC, 499, and 498), Graduate Students, and Postdoctoral Fellows
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Last Modified:2011-04-19 |