Developmental 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 and 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 …

Neural Development To Neurodegeneration Through The Mind Of A Worm, Miranda Arnold

Master of Science in Integrative Biology Theses

Defects in the nervous system can impact the normal function of an organism. By examining mutations during neuronal development, we can better understand the significance of specific pathways. The EphR/ephrin pathway is crucial for axonal guidance during development. The simple organism, C. elegans, allow us to study the impact of EphR/ephrin genes on neuronal morphology, synapse connections, and basic behavior. In specific EphR/ephrin mutants, we see change in morphology and loss of synapses in a thermosensory and also a chemosensory circuit. These mutations can also lead to defects in food searching behaviors. These observations lead us to conclude that …

Epigenetic Modifications In Alzheimer’S Neuropathology And Therapeutics, Michelle Esposito, Goldie Libby Sherr

Publications and Research

Transcriptional activation is a highly synchronized process in eukaryotes that requires a series of cis- and trans-acting elements at promoter regions. Epigenetic modifications, such as chromatin remodeling, histone acetylation/deacetylation, and methylation, have frequently been studied with regard to transcriptional regulation/dysregulation. Recently however, it has been determined that implications in epigenetic modification seem to expand into various neurodegenerative disease mechanisms. Impaired learning and memory deterioration are cognitive dysfunctions often associated with a plethora of neurodegenerative diseases, including Alzheimer’s disease. Through better understanding of the epigenetic mechanisms underlying these dysfunctions, new epigenomic therapeutic targets, such as histone deacetylases, are being explored. Here …

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 …}

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …

The Effects Of Two Novel Anti-Inflammatory Compounds On Prepulse Inhibition And Neural Microglia Cell Activation In A Rodent Model Of Schizophrenia, Heath W. Shelton

Electronic Theses and Dissertations

Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits …

Neural Indices Of Vowel Discrimination In Monolingual And Bilingual Infants And Children, Yan H. Yu, Carol Tessel, Henry Han, Luca Campanelli, Nancy Vidal, Jennifer Gerometta, Karen Garrido-Nag, Hia Datta, Valerie L. Shafer

Publications and Research

Objectives: To examine maturation of neural discriminative responses to an English vowel contrast from infancy to 4 years of age and to determine how biological factors (age and sex) and an experiential factor (amount of Spanish versus English input) modulate neural discrimination of speech.

Design: Event-related potential (ERP) mismatch responses (MMRs) were used as indices of discrimination of the American English vowels [ε] versus [I] in infants and children between 3 months and 47 months of age. A total of 168 longitudinal and cross-sectional data sets were collected from 98 children (Bilingual Spanish–English: 47 male and 31 female …

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 …

Forgotten Children & Bonds That Heal: The Critical Nature Of Attachment, August Ashbaker

Lesley University Community of Scholars Day

Human attachment is one of the most critical factors in proper neurological and physiological development. Attachment is built through the mutuality of emotional impact, as well as the regular reception of physical touch. Infants and children who have been deprived of these vital necessities through the lacking initiatives of their caregivers—through neglect—display visible signs of its physiological, cognitive, emotional, and behavioral impact. Research has found neglect to be the highest risk factor for permanent damage to brain development in comparison to other forms of complex trauma (i.e. chronic caregiver interpersonal trauma in childhood); it is also the most prevalent …

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 …

Nell2 Regulates The Contralateral-Versus-Ipsilateral Visual Projection As A Domain-Specific Positional Cue, Chizu Nakamoto, Elaine Durward, Masato Horie, Masaru Nakamoto

Biology Faculty Publications

In mammals with binocular vision, retinal ganglion cell (RGC) axons from each eye project to eye-specific domains in the contralateral and ipsilateral dorsal lateral geniculate nucleus (dLGN), underpinning disparity-based stereopsis. Although domain-specific axon guidance cues that discriminate contralateral and ipsilateral RGC axons have long been postulated as a key mechanism for development of the eye-specific retinogeniculate projection, the molecular nature of such cues has remained elusive. Here, we show that the extracellular glycoprotein Nell2 (neural epidermal growth factor-like-like 2) is expressed in the dorsomedial region of the dLGN, which ipsilateral RGC axons terminate in and contralateral axons avoid. In Nell2 …

A Developmental Study Of Apoptotic Markers And Histamine In Cephalopod Statocysts, Samantha Nicole Leef

Honors Theses and Capstones

Cephalopods can participate in complex navigation using landmarks that show context due to their statocysts. Statocysts are analogous to the vertebrate vestibular and auditory system encased in cartilage rather than bone making them more easily accessible. Age and anatomical dysfunctions are the reasons for many human vestibular malfunctions. Two of these sources are endolymph hydrops and aging. In the past, endolymph pressure changes were attributed to the ineffectual ion transport. Recent studies have illuminated the possibility of histamine receptors in the semicircular canal could be responsible for patients’ endolymph pressure changes rather than the previous belief that the pressure changes …

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 …

Characterizing The Cellular Nature Of The Physical Interactions Necessary For Collective Neuron Migration, Rebecca Vareed

Theses and Dissertations

Neuronal migration is an essential process in the development of the nervous system. Neurons are born in one location and migrate sizable distances to their final location. In many other developmental processes, cells migrate as collectives, where the migration of one cell influences the migration of another cell; this process has yet to be shown in the developing central nervous system. Using the conserved tangential migration of facial branchiomotor neurons (FBMNs), I aim to determine the nature of the collective migration in the developing nervous system. Here, two models of FBMN collective migration are tested: the “Pioneer” model, where following …

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 …

Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neural circuit formation is a complex process involving coordinated communication between neurons, glia and vascular-associated cells (VACs). Each cell type is responsible for a unique transcriptional and translational contribution to tissue maturation. Deciphering the intercellular signaling patterns which guide neural circuit formation during normal development is thus an essential step in understanding which components of neural circuit formation go awry in neurodevelopmental disorders. The medial nucleus of the trapezoid body (MNTB), located in the auditory brainstem, was used as a model system to study the dynamics of neural circuit formation because it contains a mostly homogeneous population of postsynaptic neurons …