Developmental Neuroscience Commons^™

P120-Catenin Subfamily Members Have Distinct As Well As Shared Effects On Dendrite Morphology During Neuron Development In Vitro, Maxsam Donta

Dissertations & Theses (Open Access)

Proper dendrite morphology is essential for neuronal connectivity and function, and abnormal dendrite morphology is seen in many neurological pathologies. This study characterizes and compares the effects of a group of four proteins – the p120-catenin subfamily – that regulate cytoskeletal remodeling and dendrite morphology. To do this, I tracked the endogenous localization of each p120-subfamily catenin during neuron development, and I determined how altering the expression of each p120-subfamily catenin affects dendrite morphology. I find that all catenins are expressed in dendritic processes and the soma, ARVCF-catenin is expressed at relatively high proportions in the nucleus, and p120-catenin and …

Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen

Theses & Dissertations

Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Biology - All Scholarship

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Honors Capstone Projects - All

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

A Novel Switch-Like Function Of Delta-Catenin In Dendrite Development, Ryan Baumert

Dissertations & Theses (Open Access)

The formation of neuronal networks in the brain is tightly regulated, and dependent on the morphology of dendrites, the branch-like signal-receiving structures extending from neurons. Disruptions in dendrite development, or dendritogenesis, can lead to the atypical neuronal connectivity associated with multiple neurodevelopmental diseases. My research addresses molecular processes that underlie dendritogenesis via analysis of a pair of novel interactions involving the protein delta-catenin.

In neurons, delta-catenin localizes to dendrites and synapses, where it functions in their development and maintenance. Structurally, delta-catenin possesses a central Armadillo domain and a C-terminal PDZ-binding motif. This motif associates with PDZ domain-containing proteins, and is …

Polarity And Competition In The Development Of The Calyx Of Held Terminal In The Medial Nucleus Of The Trapezoid Body In The Mouse, Paul Steven Holcomb

Graduate Theses, Dissertations, and Problem Reports

In the auditory brainstem, the connection between globular bushy cells of the anteroventral cochlear nucleus and principal cells (PCs) of the medial nucleus of the trapezoid body (MNTB) is created by one of the largest nerve terminals in the central nervous system, the calyx of Held (CH). The characteristics of the CH:MNTB connection—a short developmental period (48-72 hours), accessibility for recording from pre- and postsynaptic components, and clear monoinnervated end point—make this system an ideal model system for studying nervous system development. Model systems undergo stereotyped stages of development, including exuberant overinnervation, competition between terminals, and a refinement of innervation …

A Role For Δ-Catenin In Synaptic Regulation, Li Yuan

Theses & Dissertations

The cadherin-catenin complex regulates cell-cell adhesion and signal transduction in epithelial cells. It is becoming increasingly evident that components of the complex regulate various aspects of neuronal architecture and function. δ-catenin is a cytosolic component of the cadherin-catenin complex and is predominantly expressed in the central nervous system. Loss of CTNND2, which encodes δ-catenin, is associated with intellectual disability and mutations in CTNND2 have been identified in autism, suggesting that δ-catenin is a critical component of the molecular machinery underlying neural circuit function. We have previously demonstrated that δ-catenin regulates multiple aspects of synaptic and dendritic development, including dendritic …