Cell and Developmental Biology Commons^™

Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer

Honors Scholar Theses

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …

Uncovering Novel Small Regulatory Rna In Protostome, Sweta Khanal

Dissertations

Small RNAs play pivotal roles in post-transcriptional gene regulation across diverse phylum of protostomes. In this study, we investigate the functional significance of atypical miRNAs, mirtron miR-1017 in Drosophila. Through ectopic expression in neuronal cells, we demonstrate that miR-1017 extends lifespan by targeting its host transcript, acetylcholine receptor Dα2, and influencing its splicing. This novel trans-regulatory function suggests a mechanism for mirtron evolution, highlighting the interplay between splicing and post-transcriptional regulation. Additionally, we profile small RNA populations in the polychaete developmental model Capitella teleta, shedding light on the small RNA landscape in annelid worms. Our analysis reveals a rich …

Sufu In Shh Signalling Mediated Myogenesis, Suleyman Abdullah

Electronic Thesis and Dissertation Repository

Myogenesis is defined as the formation of skeletal muscle tissue during embryonic development and involves a multitude of cellular signalling pathways. Among these include the Sonic hedgehog (Shh) signalling pathway which must be deactivated for differentiation into muscle cells to occur. However, less is known regarding the pathways operation during cell differentiation and whether Suppressor of Fused (SUFU), the protein inhibitor of Shh signalling, plays a role. To address this, mouse C2C12 myoblast cells were utilized as a model and differentiated into muscle cells to identify the presence of SUFU during this time. Experiments in qRT-PCR show a decrease in …

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …

Genetic Regulation Of Müllerian Duct Regression, Malcolm Moses

Dissertations & Theses (Open Access)

Mammals, including humans, develop progenitor tissues for both male and female reproductive tract organs before they fully differentiate into a male or female tract. The progenitor tissue for the male reproductive tract is known as the Wolffian duct (WD), and the progenitor tissue for the female reproductive tract is the Müllerian duct (MD). The WD further differentiates into the vas deferens, epididymis, and seminal vesicle, while the MD differentiates into the oviduct, uterus and upper vagina. An essential step in sex differentiation for males is the regression of the MD. This regression initiates with anti-Müllerian hormone (Amh) transcription …

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2^-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2^-/- littermates at three postnatal age ranges (P8-12, P18-21, and …

Save The Frogs, Mackenzie Johnson, Alison Bohlen, Andie Ellis, Ryan Pinto

Student Work

The species Xenopus laevis is native to sub saharan Africa, but ever since its discovery in effectiveness in pregnancy tests, the frog now lives invasively around the world. Today the Xenopus Laevis is used mostly in laboratories as a model organism for studying developmental biology (Willigan 2001). The commercialized herbicide Atrazine, has been found to interact with this model organism species in an odd way you might not have guessed (Sanders 2010). Atrazine is primarily absorbed in the gastrointestinal tract and has been shown to have neuroendocrine, reproductive, and developmental effects on experimental animals such as Xenopus laevis (ATSDR 2004). …

An Analysis Of The Involvement Of Toll Receptors In Cell Movements During The Elongation Of Tribolium Castaneum, Kathryn Russell

Senior Theses and Projects

Elongation of the anterior/posterior body axis is a critical part of embryonic development. Cell movements are known to play a significant role in embryo elongation in the red flour beetle Tribolium castaneum. In the arthropod model organism, Drosophila, Toll receptors have a demonstrated role in the elongation of the embryo by driving convergent extension, in which rows of cells intercalate with one another in one direction to extend tissue in the other. In Drosophila, Toll receptors are a link between anterior-posterior patterning genes expressed in discrete stripes and effector molecules causing cell movements. This cell movement is caused …

Developmental Staging And Morphological Comparisons Of Four Fern Gametophyte Species From The Santa Monica Mountains, Tristan Furlong

Seaver College Research And Scholarly Achievement Symposium

The fern life cycle alternates between two distinct phases: a diploid sporophyte phase consisting of the “adult” fern, and a haploid gametophyte phase. Early events and changes in gametophyte development can have considerable consequences in the morphologies of these different fern species and may facilitate the various adaptive strategies employed by the gametophytes in their different habitats. This study investigates early developmental events in the gametophytes of four different fern species found in the Santa Monica Mountains, Adiantum jordanii (chaparral understory, summer deciduous sporophyte), Woodwardia fimbriata (riparian stream), Dryopteris arguta (chaparral understory, evergreen), and Pentagramma triangularis (chaparral understory, resurrection sporophyte). …

Spatiotemporal Characterization Of The Prr12 Paralogues In Zebrafish, Renee Jeannine Resendes

Electronic Thesis and Dissertation Repository

Pathogenic variants in the human PRR12 (Proline Rich 12) gene are associated with PRR12-related Neuroocular Syndrome. However, little is known about the gene/protein function. The zebrafish was utilized to address this, as its attributes place it as a premier model to study genes involved in human development and disease. In situ hybridization and RT-PCR of embryos and larvae, and qRT-PCR of adult tissues revealed the spatial and temporal distributions of the prr12 paralogues: prr12a and prr12b. Both paralogues were detected from the maternal and zygotic transcriptomes in a global and diffuse expression pattern, and there was enrichment …

The Role Of Shoc2 In Embryonic Development, Rebecca G. Norcross

Theses and Dissertations--Molecular and Cellular Biochemistry

The canonical ERK1/2 signaling cascade regulates cellular functions critical in vertebrate embryonic development such as proliferation, apoptosis, differentiation, and migration. Thus, its signals are controlled by a variety of mechanisms. Scaffold proteins are considered central to the mechanisms regulating the transmission of the ERK1/2 signals. Yet, their functions in development nor the molecular mechanisms by which they exert their control are not well understood.

This study focuses on the essential regulator of ERK1/2 signals during development – the scaffold protein Shoc2. Loss of Shoc2 leads to early embryonic lethality in mice and zebrafish. Germline mutations in the shoc2 gene result …

Investigating The Role Of Chd7 And Sox11 In Retinal Cell Development And The Ocular Complications Of Charge Syndrome, Laura Krueger

Theses and Dissertations--Biology

Proper formation of the visual system requires the precise interaction of several embryonic cell lineages, including the neuroectoderm (forms the retina and retinal pigment epithelium), surface ectoderm (forms the lens), mesoderm and cranial neural crest cells (form the ocular blood vessels and anterior ocular structures). When this process is disrupted structural birth defects such as coloboma result, leading to pediatric visual deficits. Ocular developmental defects are often present in larger syndromic disorders. One example is CHARGE syndrome, a genetic disorder characterized by coloboma, heart defects, choanal atresia, growth retardation, genital abnormalities, and ear abnormalities. Pathogenic variants in CHD7 have been …

The Transcription Factor Nfe2l2a Is Required For Development Of Hematopoietic Stem Cells In The Zebrafish Embryo, Sivam Bhatt, Teerth Patel, Madeleine Seputro, Anubhav Thapaliya, Erich Damm

Undergraduate Research Posters

Hematopoietic Stem Cells (HSCs) are the self-renewing population of cells that generate all erythrocytes and leukocytes over the lifetime of a vertebrate organism. HSCs are also the therapeutic units of curative bone marrow transplants used in the treatment of blood malignancies and in gene therapy for genetic blood disorders. In all vertebrate embryos, HSCs originate from the floor of the embryonic dorsal aorta during the endothelial to hematopoietic transition. Nascent HSCs will bud into the blood vessel and be carried to maturation sites by the embryonic blood flow. Despite the curative potential of HSC transplants in blood disorders, this approach …

Deoxyribose Phosphate Aldolase Is Required For Development Of Hematopoietic Stem Cells In The Zebrafish Embryo, Anubhav Thapaliya, Sanyam Patel, Teerth Y. Patel, Sivam J. Bhatt, Erich W. Damm

Undergraduate Research Posters

Hematopoietic stem cells (HSCs) are an integral part of modern biomedical research because they are precursors to all blood cell lineages in vertebrates. Further understanding of hematopoietic development will allow for improvements in the success of therapeutic bone marrow transplantation; which is a crucial treatment in management of both malignant and non-malignant blood disorders. Although HSC transplantation is curative for many blood disorders, finding compatible donors is difficult due to a need for immunologic compatibility. Consequently, recent research efforts have been directed towards generating HSCs for the patient, from the patient themselves through the directed differentiation of induced pluripotent stem …

The Effect Of Ethanol On Cellular Movements And Development In C. Elegans, Caitlin N. O'Connor

West Chester University Master’s Theses

Neural tube development, which gives rise to the central nervous system, is vital to embryonic development. Neural tube defects, like spina bifida, are serious and common congenital defects which can result in life-long medical complications. Folic acid has been used as a preventative measure for neural tube defects and has appeared to decrease the occurrences of neural tube defects. However, the mechanism behind folic acid’s role in neural tube development is unclear. Furthermore, some evidence suggests that ethanol decreases the levels of folates and folate coenzymes in the fetal brain and downregulates folic acid metabolism genes. To better understand the …

Understanding The Effects Of Embryonic Hyperglycemia On Retinal Development And Maintenance, Kayla Titialii-Torres

Theses and Dissertations--Biology

Hundreds of millions of people are affected by diabetes worldwide. Whether they are diagnosed with prediabetes or Type I or II diabetes, there are a variety of mechanisms in the pathogenesis of diabetes. Diabetes is a disease which consists of recurring states of hyperglycemia that can be difficult to manage due to either lack of insulin production or improper utilization of insulin. While these mechanisms of action differ, complications induced by diabetes occur in both poorly regulated Type I and II. Common complications of diabetes include nerve damage, kidney damage, and eye damage. Eye damage specifically is called diabetic retinopathy …

The Effect Of Twist1b And Twist2 Knockdown On Tgf-Beta Signaling Expression In Tendon Progenitors, Marinia N. Bishay

Honors Scholars Collaborative Projects

Somites are important mesoderm structures that form in regularly timed intervals from the anterior end of the paraxial mesoderm at the end of gastrulation during embryogenesis. Cells of the ventromedial portion of the somite, the sclerotome, undergo epithelial to mesenchymal transition, surround the notochord, and give rise to connective tissues of the axial skeleton including the vertebrae, tendons, and ligaments. We are interested in understanding how the sclerotome is compartmentalized into the region that makes tendons. Genes expressed in the sclerotome, twist1 and twist2, are likely involved in the downstream differentiation of sclerotome to tendon progenitors. Previous studies have shown …

Inner Ear Development And Advances In Inner Ear Organoid Formation, Paige Avery

The Cardinal Edge

The inner ear houses the cochlea which contains hair cells responsible for the transduction of sound waves. The process of forming these hair cells responsible for hearing is a complicated process consisting of many signaling factors that allow ectoderm to form into the otic placode, the otic vesicle, and finally prosensory cells such as hair cells (Schlosser, 2006). Loss of these hair cells contributes to deafness and hearing loss throughout life, and regeneration of these cells may serve as a therapeutic agent for those with irreversible damage. This review looks at the development of the otic placode and hair cells …

The Role Of Tbx2 In Germ Layer Suppression And Dorsoventral Patterning During Early Vertebrate Development, Shoshana Reich

Dissertations, Theses, and Capstone Projects

The differentiation of the three primary germ layers is precisely regulated by inductive cues, the intracellular networks through which these signals are transduced, and a broad array of nuclear proteins, such as transcription factors and epigenetic modifiers. Precise regulation of these various factors is crucial to proper development. Members of the T-box family of DNA-binding proteins play a prominent role in the differentiation of the three primary germ layers. VegT, Brachyury, and Eomesodermin function as transcriptional activators, are expressed in the presumptive mesendoderm and, in addition to directly activating the transcription of endoderm- and mesoderm-specific genes, serve variously as regulators …

Negative Regulation Of The Kinase Lin-45 By The E3/E4 Ubiquitin Ligase Ufd-2, Augustin Deniaud

Theses and Dissertations

The serine/threonine kinase BRAF is a key part of the Ras-Raf-MEK-ERK pathway, an inducer of cell growth, differentiation, and survival. In humans, activating mutations, most commonly BRAF(V600E), have been detected in several cancers, including melanoma and thyroid cancer. In the Caenorhabditis elegans ortholog LIN-45, the equivalent mutation LIN-45(V627E) results in elevated Raf-MEK-ERK signaling. We performed an unbiased genetic screen to identify negative regulators of LIN-45(V627E). Here, we report the identification of the E3/E4 ubiquitin ligase UFD-2, and show it is a negative regulator of LIN-45 protein activity and levels. Loss of UFD-2 leads to accumulation of wild-type LIN-45 protein as …

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 …

The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle

Honors College Theses

Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …

A Systematic Review Of Brainstem Contributions To Autism Spectrum Disorder, Ala Seif, Carly Shea, Susanne Schmid, Ryan A Stevenson

Anatomy and Cell Biology Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 66 children in Canada. The contributions of changes in the cortex and cerebellum to autism have been studied for decades. However, our understanding of brainstem contributions has only started to emerge more recently. Disruptions of sensory processing, startle response, sensory filtering, sensorimotor gating, multisensory integration and sleep are all features of ASD and are processes in which the brainstem is involved. In addition, preliminary research into brainstem contribution emphasizes the importance of the developmental timeline rather than just the mature brainstem. Therefore, the purpose of this systematic review …

Rab35 Centered Membrane Trafficking Pathway Directs Apical Constriction During Drosophila Gastrulation, Hui Miao

Electronic Theses and Dissertations

Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating high-tension contractile forces at the cell cortex before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be cellular processes to extract unidirectional changes that drive processive transformations in cell shape. During Drosophila melanogastergastrulation, the invagination of the prospective mesoderm is driven by the pulsed constriction of apical surfaces. Here, we address the mechanisms by which the irreversibility of pulsed events is achieved while also permitting uniform epithelial behaviors to emerge. We use MSD-based analyses to identify contractile steps and find that when a …

The Genome-Wide Roles Of The Lung Lineage Transcription Factor Nkx2-1 In The Regulation Of Opposing Cell Fates In Vivo, Danielle Renae Little

Dissertations & Theses (Open Access)

Lineage transcription factors mark, promote, and maintain multiple distinct cell types originating from a common progenitor. Despite their essential role, how such factors function and bind genome wide to orchestrate the epigenetic changes necessary to form and maintain these identities in vivo is unclear. One lineage transcription factor NK Homeobox 2-1 (NKX2-1) is expressed throughout the lung epithelium during development and was thought to be lost in the extraordinarily thin cell type required for gas exchange– the alveolar type 1 (AT1) cell. Complementing precise genetic knockouts with cell type-specific ChIP-seq, ATAC-seq, and scRNA-seq, our study shows that AT1 and AT2 …

The Role Of Cdx4 During Patterning Of Definitive Hemogenic Mesoderm, John Philip Creamer

Arts & Sciences Electronic Theses and Dissertations

The current standard of treatment for a variety of hematopoietic malignancies and genetic disorders is allogenic bone marrow transplantation, where donor hematopoietic stem cells (HSCs) engraft within the host and give rise to all of them hematopoietic lineages necessary for homeostasis. In many cases, finding a compatible human leukocyte antigen (HLA) matching donor is not possible, due to the large amount of genetic variation at those loci, but with the advent of induced pluripotent stem cells (iPSCs), unlimited sources of patient matched cells can be derived. Hematopoietic differentiations of human pluripotent stem cells (hPSCs) have been shown to recapitulate the …

Fgf20 In Olfactory System And Cochlea Development, Lu Morgan Yang

Arts & Sciences Electronic Theses and Dissertations

The olfactory epithelium (OE) is a neurosensory organ required for the sense of smell. Turbinates, bony projections from the nasal cavity wall, increase the surface area within the nasal cavity lined by the OE. We identified a population of OE progenitor cells that expand horizontally during development to populate all lineages of the mature OE and increase OE surface area. We show that these Fgf20-positive, epithelium-spanning progenitor (FEP) cells are responsive to Wnt/β-Catenin signaling. Wnt signaling suppresses FEP cell differentiation into OE basal progenitors and their progeny, and positively regulates Fgf20 expression. We further show that FGF20 signals to the …

Elucidating The Functional Location Of Platelet-Derived Growth Factor Receptor Alpha, Creation Of A Review Chapter On The Use Of Zebrafish In Studying Congenital Heart Defects, And Using 3d Printing To Create Laboratory Tools, Jaret Lieberth

Honors Theses

Congenital heart defects (CHDs) are currently the most prevalent form of birth defect in the United States. Their combined frequency and severity make necessary a deeper understanding of the molecular underpinnings guiding heart formation. The first major step in cardiac morphogenesis, cardiac fusion, involves the medial movement of bilateral populations of myocardial precursor cells to the embryonic midline, where they merge to form the primitive heart tube. Although crucial to subsequent organogenesis, the precise mechanisms governing cardiac fusion remain unknown. Previous studies have found that a mutation in platelet-derived growth factor receptor alpha (pdgfra), called refuse-to-fuse (ref), results …

Evaluation Of The Bax-Vdac Interaction And Their Influence On Apoptosis In Drosophila Melanogaster, Frances Marie Gatlin

Honors Theses

Apoptosis, also known as programmed cell death, is a cellular process used for development or for when cells undergo injury or stress. The Bcl2 family of proteins includes both pro-apoptotic and anti-apoptotic proteins that control the intrinsic pathway of apoptosis. Understanding the mechanisms and influence these proteins have on apoptosis is an important area of research focused on in Dr. Jones’s lab. Evidence shows a homology amongst the Bcl2 family of proteins at the BH3 domain. Dr. Jekabsons' lab has found a potential homology amongst VDAC 1-3 and the Bcl2 family at the BH3 domain.

Specifically, our lab is using …