Developmental Neuroscience Commons^™

Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia

Honors Scholar Theses

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …

Use Of Cre-Lox Mice As A Model For Ependymogenesis, Poorva Bagchee

Honors Scholar Theses

Stem cells in the lateral ventricles of the brain undergo a process of development within the ventricular-subventricular zone. In early development neuroepithelial cells divide to form more neuroepithelial cells or convert to radial glial cells (RGCs). These RGCs, or stem cells, then divide to form neurons or other glial cells such as ependymal cells, which form a single-layered ependyma along the ventricular wall. These stem cells divide in two ways: symmetrically, producing two ependymal cells or asymmetrically, yielding one neural stem cell and ependymal cell. To further study this process the Cre-lox system in mice will be used. By breeding …

Development Of Vasculature Patterns In A Mouse Model Of Supratentorial Ependymoma, Jackson Ayers

Honors Scholar Theses

Supratentorial Ependymoma (ST-EPN) is a subtype of ependymoma, a primary solid tumor found throughout the nervous system. ST-EPN are most commonly caused by an oncogenic fusion between the zinc finger gene ZFTA and the RELA, and this distinct ependymoma subtype is readily modeled in mice by conditional expression of ZFTA-RELA in radial glial cells. ST-EPN are known to have a distinctive arrangement of tumor cells and vasculature forming pseudo-rosettes in which polarized tumor cells surround blood vessels within the tumors. It is not known how these pseudo-rosettes or the tumor vasculature form and develop in ST-EPN, so in this study …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Reorganization Of The Human Ventricular-Subventricular Zone Neural Stem Cell Niche In Fetal-Onset Hydrocephalus, Saurabh Kumar

University Scholar Projects

Fetal-onset hydrocephalus is a relatively common birth defect occurring in 1-2 cases per thousand births and is characterized by abnormally expanded brain ventricles. Current diagnosis for this complex pathology often involves relatively simple metrics and heavy reliance on clinician experience over objective measures. Those affected often suffer chronic headaches and cognitive deficits and may present with a bulging skill. Shunting is considered the standard treatment for communicating hydrocephalus (i.e. cerebrospinal fluid flow is physically unobstructed in the ventricular system). Shunting remains a highly invasive procedure often performed during the critical period of infancy and has a high failure rate of …

Amygdala And Neocortical Structural Volume Analysis In The Shank3b Mutant Mouse Model Of Autism Spectrum Disorder, Preet Sawhney

Honors Scholar Theses

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by abnormal social behavior, deficits in communication, and motor stereotypy. The SHANK3 gene, responsible for the generation of a scaffolding protein that is integral for the development of synapses, has been identified as one of the primary candidate genes implicated in the disorder. Shank3B is the rodent homolog for this gene. Research has shown that when this gene is disrupted in rodent models (e.g., via knock-out (KO)), ASD-like behaviors result. These include deficits in social interaction, increased anxiety, and repetitive self-grooming. The current study aimed to identify a physiological …

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 Ush2a Gene: An Analysis Of Ultrasonic Vocalizations In A Mouse Model Of Usher Syndrome Type 2, Kiana R. Akhundzadeh

Honors Scholar Theses

Usher syndrome type 2 is a complex autosomal recessive genetic disorder that is characterized by moderate to severe congenital sensorineural hearing loss, the onset of retinitis pigmentosa in the second decade of life, and in some cases, vestibular dysfunction. Mutations in the USH2A gene account for 85% of cases of type 2. The USH2A gene is responsible for encoding the protein usherin, which has an important role in the development and function of inner ear hair cells and retinal photoreceptors. Until recently, it has been believed that carriers of the USH2A mutation were phenotype free. However, recent data has suggested …

Neurostructural Organization And Neocortical Projecting Neuron Distribution In A Mouse Model Of Timothy Syndrome-Mediated Autism Spectrum Disorder, Aiden L. Ford

Honors Scholar Theses

Aims: This study investigates the nuanced effect of the CACNA1C mutation on neurocognition and neurodevelopment via an extended study of the Timothy Syndrome (TS) mediated Autism Spectrum Disorder (ASD) mouse model – TS2-neo. It includes: (1) an expanded assessment of the TS2-neo behavioral phenotype, and (2) a comprehensive histological analysis of cortical structural and laminar features.

Methods: 24 age-matched male mice – 12 TS2-neo (B6.Cg-Cacna1c^tm2Itl, knock-in G406R mutation), 12 WT (C57BL/6J) – were tested on paradigms examining motor, socio-communicative and cognitive abilities. Neural tissue was processed for either volumetric analysis through Nissl stain (8 TS2-neo, 8 WT) or …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

University Scholar Projects

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

Honors Scholar Theses

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …

Characterization Of The Ependymal Barrier Due To Human Aging And Injury In Murine Models, Ye Sun

University Scholar Projects

Ventriclulomegaly, or the expansion of the ventricles in the brain, is a phenomenon associated with age and injury to the brain. The ependymal layer that encases the ventricles displays certain degrees of plasticity and regenerative ability due to its associated stem cell niche, the subventricular zone (SVZ). Previous research in the Conover Lab has shown that in the mouse, which maintains an actively proliferating SVZ into adulthood, there is an intact ependymal monolayer throughout normal aging, with maintained lateral ventricle size with some degree of stretching. In contrast, the human SVZ declines in proliferative capacity after infancy, and age-related changes …

Effects Of Neonatal Hypoxic Ischemic Brain Injury On Spatial Working Memory, Amanda L. Smith

Master's Theses

Children born prematurely or at very low birth weight (VLBW) have an increased risk for hypoxic ischemic brain injury (HI). HI refers to a lack of adequate blood and oxygen flow in the brain. HI can also occur in the term infant due to birth complications such as prolonged labor, placental dysfunction, or cord prolapse. In both populations (though exact patterns of neuropathology vary) brain damage is likely to occur in the form of decreased hippocampal and cortical volume, and enlargement of the ventricles (Kesler et al., 2004, Nagy et al., 2009). Resulting neuropathology can in turn lead to cognitive …

Diffusion Barriers Of The Lateral Ventricular System, Anitha Saravanakumar

Master's Theses

Adult neurogenesis in mammalian brain has become a well-accepted phenomenon. The neural stem cells in the sub ventricular zone (SVZ) along the lateral wall of the lateral ventricle, the largest germinal center of adult neurogenesis, are maintained by the neural stem cell niche. One prominent feature of the niche is its close proximity to the cerebral spinal fluid (CSF). The role of micromolecules (such as ions, water and gases) present in the CSF and diffusing through the lateral ventricular wall and how the stem cell micro-environment is maintained is poorly understood. The cytoarchitecture of the lateral ventricular wall with a …

Investigation Of Mirnas Expression In A Citron-Kinase Mutant Model Of Microcephaly, Shan Parikh

Master's Theses

Mutation of Citron-Kinase (Cit-K) in rodents causes substantial reductions in the number of neurons generated in the CNS and results in a primary microcephaly-like phenotype. Evidence from drosophila genetics has further established a genetic link between Cit-K and a protein Argonaut 1 (AGO1), which is required for proper functioning of the miRNA machinery (2). Experiments characterizing the role of miRNAs in the developing cortex demonstrate the requirement of miRNAs for differentiation of neural progenitor cells starting at embryonic day 12.5 (3). Together, this evidence links the role of miRNAs to neurogenesis and thus this relationship warrants further investigation. Here miRNA …