Molecular and Cellular Neuroscience Commons^™

Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen

Theses & Dissertations

Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …

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 …

Micrornas Are Necessary For Bmp-7-Induced Dendritic Growth In Cultured Rat Sympathetic Neurons, Vidya Chandrasekaran

Vidya Chandrasekaran

Investigation Of Even-Skipped, A Developmentally-Regulated Gene Controlling Neural Segmentation In Dragonflies, Kathryn Bangser

Honors Theses

A comprehensive understanding of the genetic mechanisms underlying pattern formation and neurogenesis is necessary in order to trace the evolutionary history of insect embryogenesis.

One of the most important processes of embryogenesis is the organized pattern formation that allows for proper body segmentation and neural development. Proper segmentation, which relies on a series of specific gene expressions, is necessary for the development of an operational nervous system. Even-skipped (eve), one such regulatory gene, has been studied extensively in certain model organisms, and theories regarding the evolution of its functional role could be further elucidated by visualizing its expression …

Investigating The Role Of Integrin Beta 3 In Dendritic Arborization In The Supragranular Developing Cerebral Cortex, Zachary Logan Holley

Senior Honors Projects, 2010-2019

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 …

Notch Inhibitors And The Bet Inhibitor Jq-1 Decrease The Growth Of Primary Tumor Cells Derived From A Novel Mouse Model Of C11orf95-Rela Induced Brain Tumor, Ericka Randazzo, Jesse Dunnack, Justin Fang, Joseph Loturco Phd

University Scholar Projects

Brain tumors are the most common childhood solid malignancy, and because of remarkable advances in treating many cancers outside of the brain, they have become the leading cause of cancer mortality in children. Ependymomas are a class of brain tumors which can be further subdivided into three groups based upon their location and genetic features. Of the three classes, supratentorial ependymomas are the only subgroup known to be marked by an oncogenic driver gene, which consists of a fusion mutation between the C11orf95 and RELA genes. C11orf95-RELA positive tumors are the most aggressive and lethal of …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Circadian Rhythmicity And Neurodevelopment Of Disco And Grim Mutations In Drosophila Melanogaster, John Patrick Story

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

The death gene grim and its pathway for apoptosis has been studied extensively in Drosophila Melanogaster. The effects of grim mutations on circadian neurodevelopment and locomotor assays have yet to be investigated. Mutations in the gene disconnected (disco) has been shown to disrupt the normal development of the circadian circuitry, specifically the small ventro-lateral neurons (s-LNv’s). Which has shown to severely decrease rhythmicity during free-running periods. Alternatively, we have observed an increase in rhythmicity during free-running periods in grim mutations. Our goal is to investigate the neurodevelopment of the circadian circuitry and their associated locomotor activities in these Drosophila mutations.

The Role Of Ash1l During Human Neurodevelopment, Anna Bagnell

Senior Theses

Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and are highly heritable. A significant proportion of ASD cases are of complex genetic etiology; complexity which might reflect the impact of gene-environment interactions. However, there is a gap in our understanding of the mechanisms that underlie the gene-environment interaction in autism complex etiology. Genome wide association studies in large ASD cohorts identified high risk variants associated with autism in genes that regulate histone modifications and remodel chromatin. These findings highlight the relevance of chromatin regulatory mechanisms in the pathology of ASD. Changes in Histone H3 methylation have been …

The Integration Of Multiple Sources Of Sonic Hedgehog In The Spinal Cord Contribute To The Production Of First-Born Oligodendrocyte Precursor Cells Which Become Critical For Synapse Remodeling In Response To Adult Motor Neuron Injury, Lev Starikov

Dissertations, Theses, and Capstone Projects

Oligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here I show that interrupting Sonic hedgehog (Shh) signaling originating from nascent ventricular zone derivatives (VZD), motor neurons and the lateral floor plate, almost completely blocks ventral but not dorsal oligodendrogenesis without noticeably affecting early tissue patterning and embryonic development. In the absence of ventral OPCs, dorsal OPCs increase proliferation and populate the entire spinal cord with increased density. In these mutant mice, dOPCs take …

Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, Diego F. Buenaventura

Dissertations, Theses, and Capstone Projects

There are two types of photosensitive cells of the retina that contribute to image formation: Cone photoreceptors that mediate color discrimination and rods that provide photosensitivity in low-light conditions. Given the importance of cones in high acuity and color vision, deficiencies in this cell type that result from ailments such as retinitis pigmentosa and macular degeneration can lead to a debilitating loss of vision. Currently, one of the most pressing goals in the field of retinal development is the elucidation of the gene regulatory networks (GRN) involved in inducing an undifferentiated cell into becoming a functional cone photoreceptor.

Recently, an …

Evidence-Based Probiotic Intervention For Behavioral And Social Deficits In Autism Spectrum Disorder, Allisen To

Scripps Senior Theses

Autism Spectrum Disorder (ASD) refers to a heterogeneous neurological condition characterized by repetitive and restrictive behaviors and social communication deficits. ASD diagnoses are at a record high, at approximately 1 in 59 children according to the US Center for Disease Control. Currently, there are no available interventions that effectively treat the core symptoms of ASD. All pharmaceutical options address comorbid side effects of ASD but not core deficits and are particularly associated with negative side effects. Additionally, there are economic and geographic barriers that can prevent families of individuals with ASD from seeking or receiving effective interventions. Many of the …

M1 Melanopsin Ganglion Cells In The ​Mus Musculus​ Retina Are Similar In Shape And Size, Geoffrey K. Sarpong

Williams Honors College, Honors Research Projects

An M1 melanopsin retinal ganglion cell (mRGC) is a subtype of the five melanopsin ganglion cells. The M1-type mRGC is distributed on the dorsal retina of a mouse and has an extensively overlapping dendritic network in both the sublamina a (OFF) and sublamina b (ON) layers of the inner plexiform layer. In the dorsal retina, the M1-type mRGCs are distinct and asymmetric.

The aim of this study was to examine the morphological similarity (shape and size) of M1-type mRGCs. The study traced 20 neurons in the first four months of a glaucoma retina of a DBA mouse, made measurements of …