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Date of Award
Bachelor of Science (BS)
Department of Biology
Integrin subunits have been implicated in axonal and dendritic outgrowth. In particular, a strong positive association has been found between mutations in integrin beta 3 (Itgb3) and autism spectrum disorder, but little is known about neuronal Itgb3 function in vivo. Many forms of autism spectrum disorder are thought to arise from dysfunctional dendritic arborization and synaptic pruning. Global knockout of Itgb3 in mice leads to autistic-like behaviors. Itgb3-/- mice also have reduced callosal volume, a key neuroanatomical correlate of autism. Here, we test the hypothesis that Itgb3 is required for normal dendritic arborization in layer II/III pyramidal neurons of mouse neocortex. This was achieved by causing Itgb3 loss of function through Cre-lox-mediated excision of Itgb3 in a subset of layer II/III cortical neurons. Layer II/III cortical neurons were targeted for excision via in utero electroporation of GFP/Cre DNA constructs to the ventricular zone of developing telencephalon of mice in which exon 1 of Itgb3 is flanked by loxP sites. Laminar positioning, regional targeting, and dendritic arborization of targeted neurons in juvenile mice (P23) were analyzed. Male and female mice were used for the study and analysis was blind to genotype. Results point to aberrant basal dendritic arborization of mutant neurons, when compared to C57BL6/J controls. Thus, integrin beta 3 appears to regulate basal dendritic arborization of layer II/III pyramidal neurons in the developing neocortex.
Holley, Zachary Logan, "Investigating the role of integrin beta 3 in dendritic arborization in the supragranular developing cerebral cortex" (2019). Senior Honors Projects, 2010-current. 682.
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