Student Theses and Dissertations

Date of Award

2006

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Strickland Laboratory

Keywords

laminins, laminin gamma 1, cerebral cortex development

Abstract

Laminins are a major component of basement membranes, including those in the central nervous system (CNS). To explore the role of laminin γ1, a subunit common to all laminins found within the CNS, we developed a murine model in which laminin γ1 is conditionally disrupted in the nervous system. These mice show cortical developmental abnormalities including undulations in the embryonic cortical plate and resultant adult cortical layers and abnormal positioning of pyramidal neurons and interneurons. We have investigated the mechanisms underlying these abnormalities. Neuronal migration via the establishment of the radial glial scaffold and the Cajal-Retzius cell layer was affected in the mutants. Furthermore, axon pathfinding was impaired with developing axons projecting along the abnormally structured cortical plate. Laminin γ1 also plays a role at the cellular level, as disturbances in normal neuronal morphology were observed in mutant animals, but laminin was not required for cell survival or cell proliferation. These data indicate a fundamental role for laminin γ1 in both the cellular and structural development of the cerebral cortex.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy

Permanent URL

http://hdl.handle.net/10209/228

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