Uniform TitleNovel developmental roles of EphA receptors
NameCooper, Margaret Ann (author), Zhou, Renping (chair), Wagner, George (internal member), Crockett, David (internal member), Mason, Carol (outside member), Cai, Li (outside member), Rutgers University, Graduate School - New Brunswick,
Central nervous system,
DescriptionThe EphA tyrosine kinase receptors mediate diverse cellular functions including axon guidance, cell migration, cell adhesion, and differentiation. A member of this family, EphA5, is well known for its roles in the development of several topographical maps in the CNS such as the hippocamposeptal, thalamocortical, and retinotectal systems. However, the EphA5 receptor is expressed beyond just these few areas, for example, in the olfactory bulb, hypothalamus, amygdala, and cranial nerve ganglia. In providing a thorough analysis of EphA5 receptor localization in developing and adult mice, previously unexplored regions with EphA5 expression were uncovered. Functions of the EphA receptor and A-ephrins were characterized in further studies in two of these areas, the midbrain dopaminergic nuclei in the ventral midbrain and the lens of the eye.
Expression patterns of EphA5 in the midbrain and of ephrin-A5 in the striatum, suggested a role in mediating dopaminergic axon-target interactions. Dopaminergic neurons adhere to striatal tissue in part through ephrin-A5 functions. An examination of the biological effects of ephrin-A5 on dopaminergic neurons revealed enhanced neurite outgrowth in the presence of the ligand in vitro. Additionally, retrograde tracing studies with ephrin-A5-/- mice revealed that fewer neurons sent axons to their appropriate striatal targets, indicating that interactions between ephrin-A ligands and EphA receptors may promote the proper development of the midbrain dopaminergic pathways.
Outside of the nervous system, a second novel role for EphA receptors was identified in the lens. Ephrin-A5-/- mice exhibited a high incidence of cataract development. Of several EphA receptors shown to be expressed in the lens, EphA2 exhibited decreased phosphorylation in ephrin-A5-/- lenses demonstrating that it could function as a physiological receptor for the ligand. Although the mechanism for the defects is unclear, electron micrographs showed disruptions in the plasma membrane junctions between lens fiber cells. Early signs of lens degeneration in mutant mice consisted of the formation of small vacuoles and a loss of fiber cell shape. Both of these studies demonstrate the positive functions mediated by the Eph family.
NoteIncludes bibliographical references (p. 151-166).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.