Date of Award

8-3-2009

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Charles Greer

Second Advisor

Anne Williamson

Abstract

THE ROLE OF FRIZZLED-1 AND FRIZZLED-3 IN OLFACTORY SENSORY NEURONAL TARGETING. Mina G. Safain. Department of Neurosurgery, Yale University School of Medicine, New Haven, CT. While most areas of the brain do not exhibit profound neurogenesis or continuing synaptogenesis in the adult, there are notable exceptions which include the olfactory and hippocampal regions of the nervous system. In the olfactory system the olfactory sensory neurons continually turn over and extend their axons into the olfactory bulb in a highly precise manner. Some preliminary data exists that suggests the presence of Wnt and Frizzled (Fz) family members in the primary olfactory pathway. Recent evidence has suggested that these proteins could function as guidance cues but these proteins have not been studied in the olfactory system. Therefore this family of proteins, including Fz-1 and Fz-3, could have a role in olfactory sensory neuron targeting. This study proposes to test the hypothesis that the expression pattern and temporal regulation of Fz-1 and Fz-3 is consistent with a role in olfactory sensory neurons axon targeting. Mouse embryos at ages E10, 10.5, 11, and 13 (E0 is the day of conception) were removed, fixed, sectioned on a cryostat, and then thaw mounted onto slides. Immunohistochemistry was performed on the sections and labeled with antibodies for either Fz-1 or Fz-3 and a variety of other antibodies that labeled mature and immature olfactory sensory neurons (GAP 43, NCAM, PSA-NCAM, OCAM, ß-Tubulin). Nuclear staining was accomplished by using DRAQ-5. Stained sections were analyzed with a confocal microscope. Fz-1 and Fz-3 were present as early as embryonic day 10-10.5 and expression increased dramatically over the next 3 days of development. These receptors also colocalized with both markers of mature and immature olfactory sensory neurons. These proteins seem to be upregulated and expressed more heavily on olfactory sensory neurons during the onset and throughout the period that is essential for proper glomerular targeting. It is therefore likely that these proteins are involved in some aspect of olfactory sensory neurons intricate navigation from the olfactory epithelium into the glomerular layer of the developing olfactory bulb.

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