Cell and Developmental Biology Commons^™

Insights Into The Role Of Sox6 In The Developing Heart, Hannah Tarolli

MUSC Theses and Dissertations

Approximately 40,000 babies born each year in the U.S. have a congenital heart defect (CHD). However, only a small percentage of CHDs has a known genetic cause, highlighting the need for research surrounding heart development and the pathogenesis of CHDs. Heart development research aims to elucidate the precise coordination of gene expression and cell signaling with the goal of advancing prevention and treatment methods. During heart development, cells from several origins play a crucial role. This includes cells derived from the endocardium, epicardium, cardiac neural crest, and second heart field. Previous studies have revealed that the transcription factor, SOX9, is …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

The Myopia Epidemic: Integrating Genetic, Environmental, And Epigenetic Pathways To Define A Critical Window For Intervention, Pranavika Balaji

Undergraduate Research Posters

Myopia, or nearsightedness, has increased rapidly worldwide and is now a major public health concern caused by both genetic and environmental factors. Current understanding shows that too much near work, limited time spent outdoors, and prolonged screen use contribute to abnormal eye growth in individuals who may already have a genetic predisposition. At the molecular level, epigenetic changes and shifts in DNA activity, often influenced by environmental conditions, affect the signaling pathways that regulate eye development and may help explain why myopia is increasingly common among children. This paper synthesizes recent environmental, genetic, and epigenetic research to explain how these …

Retinal Precursor Cell Enriched Multiomic And Pseudo-Time Analysis Of Developing And Reprogrammed Photoreceptors, Brendon M. Patierno

Dissertations, Theses, and Capstone Projects

The vertebrate retina is a complex tissue made up of seven major cell subtypes which during development must differentiate and localize into a highly organized structure. These neuronal cells do not regenerate if damaged or diseased, and the progressive deterioration of cone photoreceptor cells is the leading cause of age related blindness. Currently there are no cures for this disease, but one promising therapeutic avenue is cell transplantation research. If we can further elucidate the gene regulatory networks that define cone cell development, this knowledge could be applied to the generation of healthy cone cells in clinically relevant models.

The …

Analysis Of An Ethanol Sensitive Bmp-Nkx2.3-Fgf Signaling Pathway In Pouch Morphogenesis., Hieu Dai Le Vo

Electronic Theses and Dissertations

Craniofacial malformations lie at the heart of Fetal Alcohol Spectrum Disorders (FASD). While there is growing evidence for a genetic component to FASD, little is known of the cellular mechanisms underlying these ethanol-sensitive loci in facial development. Bone Morphogenetic Protein (Bmp) signaling pathway dependent pouch formation is a key mechanism in facial development. We have previously shown that multiple Bmp mutants are sensitized to ethanol-induced facial defects. However, ethanol does not directly impact Bmp signaling. This suggests that downstream effectors, like nkx2.3 and Fibroblast Growth Factor (Fgf) signaling, may mediate the impact of ethanol on Bmp mutants. Here, I …

The Role Of Androgen Receptor And B2/Alu Sine Rna Interaction In Hippocampal Dendritic Development, Troy A. Richter

Graduate Doctoral Dissertations

Once dismissed as “junk”, transposable elements have recently gained recognition for their regulatory roles, especially in the brain. During development, circulating androgens promote proper morphological development of hippocampal neurons. We and others have shown that murine B2 SINE RNA is a regulator in the rodent hippocampus. It is unknown, however, if B2 is necessary for the proper development of hippocampal neurons. This dissertation investigates the role of murine B2 in the development of primary hippocampal neurons in combination with androgen treatment. We first examined the role of ALU SINE and androgen receptor in a prostate cancer cell model and found …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

An Analysis Of Cellular And Tissue Function Of Lipin In Drosophila Melanogaster, Judah Christian Scott

Graduate Theses and Dissertations

Regulation of energy expenditure and energy storage is a key characteristic of life. Numerous enzymes play a crucial role in regulating energy metabolism. Lipins are a highly conserved family of proteins that function in both lipid synthesis and gene regulation. In the glycerol-3 phosphate pathway, lipins act as a phosphatidate phosphatase (PAP) producing diacylglycerol. In gene regulation, lipins act as transcriptional co-regulators of metabolic genes. The enzymatic PAP activity occurs in the cytoplasm; however, for lipins to function as gene regulators, they must translocate into the nucleus. Nuclear translocation is facilitated by the nuclear localization signal (NLS) within the protein. …

From Genes To Patterns: A Framework For Modeling The Emergence Of Embryonic Development From Transcriptional Regulation, Jimena Garcia-Guillen, Ezzat El-Sherif

School of Integrative Biological & Chemical Sciences Faculty Publications

Understanding embryonic patterning, the process by which groups of cells are partitioned into distinct identities defined by gene expression, is a central challenge in developmental biology. This complex phenomenon is driven by precise spatial and temporal regulation of gene expression across many cells, resulting in the emergence of highly organized tissue structures. While similar emergent behavior is well understood in other fields, such as statistical mechanics, the regulation of gene expression in development remains less clear, particularly regarding how molecular-level gene interactions lead to the large-scale patterns observed in embryos. In this study, we present a modeling framework that bridges …

Determining Localization Of Surf-4 In Drosophila Melanogaster In The Secretory Pathway, Jada Scott

Mahurin Honors College Capstone Experience/Thesis Projects

The purpose of this research is to determine the role of the Surfeit-4 gene, or Surf-4 locus protein, during Drosophila melanogaster development. Surf-4 was identified in the Srivastava lab in a biochemical screen for proteins that associate with the basement membrane (BM): a structure needed and required for normal development and its degradation is a hallmark of tumor metastasis. Surf-4 has been predicted to function within intracellular compartments and is known to be expressed in many parts of the developing fly. We are currently determining why Surf-4 is important in development and what role, if any, it could play during …

The Role Of Wt1 In Müllerian Duct Development, Jace Aloway

Dissertations and Theses (Open Access)

WT1 is a zinc finger transcription factor widely expressed in the urogenital system. Human mutations of WT1 lead to pediatric nephroblastoma as well as frequent differences of sex development (DSDs). Previous studies have suggested that WT1 acts as an activator for Amhr2, a necessary component of typical male differentiation. We used the mouse as a model to investigate the role of WT1 in sex development, where we deleted Wt1 in the Müllerian duct (MD) mesenchyme using a novel conditional null reporter allele, Wt1 flox-RFP. This allele utilizes the Cre-lox system to delete exons 8 and 9 of Wt1 …

Size Matters: The Characterization Of Telomere Function In Germ Cell Development In Danio Rerio, Jessica Macneil

Graduate Doctoral Dissertations

Infertility is a growing problem worldwide. According to the WHO, 48 million couples across the globe suffer from infertility and many couples turn to Assisted Reproductive Technology (ART) to become pregnant. One readout of gamete quality and successful ART is telomere integrity because telomeres are necessary for chromosome movements during meiosis so that the segregation of chromosomes happens correctly. Telomeres are well known for their role in aging; however, they play an important and understudied role during meiosis. In meiosis, telomeres attach to the nuclear envelope (NE) via a protein chain spanning the NE that interacts with cytoplasmic motor proteins, …

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 …

Connecting Genotype And Phenotype: Investigating The Functional Morphology And Molecular Architecture That Influences Craniofacial Divergence Using Lake Malawi Cichlid Fishes, Leah Delorenzo

All Dissertations

Connecting genotype and phenotype to better understand how species evolve has been a goal of evolutionary developmental biologists over the last 50 years. This dissertation aims to connect genotype and phenotype of the craniofacial skeleton within the adaptive radiation of Lake Malawi cichlids to fortify our understanding of the functional, genetic, and epigenetic factors that contribute to craniofacial divergence. I start with a functional approach using 2D geometric morphometrics to assess craniofacial shape across the Lake Malawi cichlid radiation to bolster our knowledge of the bone phenotypes that are important to niche specialization and are functionally relevant. Next, I use …

Regulation Of Embryonic Eye Regrowth In Xenopus Laevis, Dylan Guerin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Regrowth of lost organs and tissues is an amazing ability that some animals possess. For regrowth to be considered full, the organism must regrow the organ or tissue to a state that is structurally and functionally similar to that which was lost. The ability of an organism to regrow lost or damaged tissue varies among animals, both in the mechanisms utilized to achieve regrowth, and in what body parts can be regrown. Potentially even closely related species can vary wildly in regenerative ability. Therefore, regenerative research can look to other tissues and organisms for direction in elucidating the mechanisms through …

Epigenetic Mechanism Of Ebp1 In Nlrp-Dependent Development, Summer Reign Moore

Graduate Theses/Dissertations

ErbB3-binding protein 1 (EBP1) helps regulate gene expression through various epigenetic modifications and is crucial for embryotic development. NLRP2 and NLRP7 are more commonly known for their roles in the immune system, however, recent research has implicated NLRP2 and 7 as critical factors in embryonic development. EPB1, NLRP2, and NLRP7 dysfunction is a known cause of recurrent miscarriages and other developmental diseases, including infertility. NLRP2 and NLRP7 are also known to affect the levels of DNA methylation, despite that they are located exclusively in the cytoplasm. However, EBP1 can be located in the nucleus and cytoplasm, and is known to …

Functional Investigation Of Shaggy, An Inhibitor Of Canonical Wnt Signaling, In The Tardigrade Hypsibius Exemplaris, Raul A. Chavarria

UNF Graduate Theses and Dissertations

Tardigrades have a highly simplified anteroposterior (AP) axis. The mechanisms that regulate the development of this secondarily simplified AP axis are not known. In many animals, the canonical Wnt (cWnt) signaling pathway regulates primary axis establishment through antagonistic interactions with inhibitors of cWnt signaling. This study investigated the roles of shaggy, an inhibitor of cWnt signaling, in regulating development in the tardigrade Hypsibius exemplaris. Gene expression patterns of shaggy and other components of the cWnt signaling pathway were analyzed alongside markers of anterior and posterior identity using Hybridization Chain Reaction in situ in H. exemplaris. RNA interference …

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 …

Microglia Refine Early Multisensory Circuits In The Lateral Cortex Of The Inferior Colliculus In A Complement-Dependent Manner, Shaida Hamidi

Masters Theses, 2020-current

Microglia cells (MGCs), the resident macrophage of the brain, play a pivotal role in synaptic pruning of newly established circuits during early critical periods. Classical complement cascade signaling enables MGCs to identify unnecessary or underutilized contacts and specifically target them for removal and subsequent degradation. Such recognition and engulfment behaviors require receptor-ligand interactions, whereby “eat me” tags (complement component 3, C3) bind their cognate receptor (complement receptor 3, CR3) expressed on MGCs. Compromised complement signaling in certain systems results in under-pruning or unrefined map configurations, and is thought perhaps to underlie certain autism-related behavioral phenotypes (e.g. sensory hypersensitivities, decreased social …

Genetic Regulation Of Müllerian Duct Regression, Malcolm Moses

Dissertations and 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 …

Molecular And Systemic Epigenetic Inheritance: Integrating Development, Genetics, And Evolution, Robert Lickliter, David S. Moore

Pitzer Faculty Publications and Research

Currently, a central problem for theoretical biology is the integration of development with genetics and evolutionary theory. Through the late 20^th century, biologists held that animals resemble their ancestors strictly because of the transgenerational transmission of DNA. This view effectively wrote development out of evolutionary biology. However, many molecular and developmental biologists now understand that phenotypes—anatomical, physiological, and behavioral traits—are not determined by genes (i.e., DNA segments) alone; instead, they emerge epigenetically from developmental processes involving co-acting genetic factors, environmental factors, molecular epigenetic factors, and other non-genetic factors within organisms’ bodies. This insight forces a rethinking of biological inheritance. …

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). …

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). …

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 …

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 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 …

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 …

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 …