Developmental Biology Commons^™

Functional Characterization Of Scaffold Protein Shoc2, Hyein Jang

Theses and Dissertations--Molecular and Cellular Biochemistry

Signaling scaffolds are critical for the correct spatial organization of enzymes within the ERK1/2 signaling pathway and proper transmission of intracellular information. However, mechanisms that control molecular dynamics within scaffolding complexes, as well as biological activities regulated by the specific assemblies, remain unclear.

The scaffold protein Shoc2 is critical for transmission of the ERK1/2 pathway signals. Shoc2 accelerates ERK1/2 signaling by integrating Ras and RAF-1 enzymes into a multi-protein complex. Germ-line mutations in shoc2 cause Noonan-like RASopathy, a disorder with a wide spectrum of developmental deficiencies. However, the physiological role of Shoc2, the nature of ERK1/2 signals transduced through this …

Zebrafish Model Of Mll-Rearranged Acute Myeloid Leukemia, Alex J. Belt

Theses and Dissertations

Acute myeloid leukemia (AML) is the second most common type of leukemia and accounts for 80% of adult acute leukemia cases and is characterized by the accumulation of poorly or undifferentiated myeloid blast cells. Standard treatment includes chemotherapy, which if unsuccessful, is followed by more rigorous chemotherapy as well as stem cell transplantation. Considering most patients are over the age of 45, these more rigorous therapies are not always possible, and as such, new therapies must be developed. Furthermore, AML patients harboring a chromosomal rearrangement involving Multiple Lineage Leukemia (MLL) that results in the expression of an MLL fusion protein …

Regulated Transcriptional Silencing Promotes Germline Stem Cell Differentiation In Drosophila Melanogaster, Pooja Flora

Legacy Theses & Dissertations (2009 - 2024)

Germ cells are the only cell in an organism that have the capacity to give rise to a new organism and are passed from one generation to the next. Therefore, to maintain this unique ability of totipotency and immortality, germ cells execute specific functions, such as, repression of a somatic program and contour a germ line-specific pre- and post-transcriptional gene regulatory landscape. In many sexually reproducing organisms, germ cells are formed during the earliest stages of embryogenesis and undergoes several stages of development to eventually get encapsulated by the somatic cells of the gonad. Once, in the gonad, the germ …

Chromatin-Signaling Axis Orchestrates The Formation Of Germline Stem Cell Differentiation Niche In Drosophila, Maitreyi Upadhyay

Legacy Theses & Dissertations (2009 - 2024)

Stem cells have the unique capability of self-renewing into stem cells and differentiating into several terminal cell types. Loss of either of these processes can lead to aging, progression towards degenerative diseases and cancers. Insight into how self-renewal and differentiation are regulated will have tremendous therapeutic impact. Drosophila is an excellent model system for stem cell study due to the availability of various mutants, markers and RNAi technology. In order to study stem cell biology, we use female Drosophila gonads, whose stem cell population – the germline stem cells (GSCs) gives rise to gametes.

Retinoic Acid Receptor Isoform-Specific Control Of Mouse Salivary Gland Development And Regeneration, Kara Desantis

Legacy Theses & Dissertations (2009 - 2024)

Controlled expansion and differentiation of progenitor cell populations is essential for organogenesis followed by continued maintenance of the population into and through adulthood. As the K5+ basal cell population is regulated by retinoic acid signaling, we interrogated the contribution of specific RAR isoforms to the regulation of these cells during submandibular salivary gland (SMG) organogenesis and regeneration. Retinoic acid has previously been shown to be involved in the development of the salivary gland, and recently, lack of retinoid signaling has been shown to impact the K5+ population of basal progenitor cells. Since retinoic acid is known to exert stimulatory effects …

Why Doesn’T A Mother Reject A Genetically Different Fetus?, Devora Krumholtz

The Science Journal of the Lander College of Arts and Sciences

Many basic multicellular organisms possess some form of immune response to protect themselves against the invasion of foreign objects. It was not until British scientist, Peter Medawar proposed a fundamental question that changed the way researchers studied the maternofetal relationship. A fetus, being genetically different from its mother should be rejected by the maternal immune system, however, it is not. Researchers have since discovered and developed several mechanisms that aim to explain how the maternal immune system prevents fetal rejection. The formation of a mechanical barrier, general and local suppression of the maternal immune system, and a shift in cytokine …

The Folic Acid Metabolism Gene Mel-32/Shmt Is Required For Normal Cell Cycle Lengths In Caenorhabditis Elegans, Kalin D. Konrad, Raquel A. Campbell, Vanessa Thiel, Jessica Sullivan-Brown

Biology Faculty Publications

Neural tube defects are common and serious birth defects in which the brain and/or spinal cord are exposed outside the body. Supplementation of foods with folic acid, an essential vitamin, is linked to a lower risk of neural tube defects; however, the mechanisms by which folic acid influence neural tube defect risk are unclear. Our research seeks to identify the basic cellular roles of known folic acid metabolism genes during morphogenesis using the roundworm Caenorhabditis elegans (C. elegans) as a simple model system. Here, we used live imaging to characterize defects in embryonic development when mel-32 is depleted. mel-32 is …

Jak/Stat Signaling Regulates Gametogenesis And Age-Related Reproductive Maintenance, Michelle Suzanne Giedt

Theses and Dissertations--Biology

Cell signaling is central to integration of internal and external cues that regulate development and homeostasis. Most development is thought of as pre-adult, but limited developmental processes occur in adults. Gametogenesis incorporates elements of both these facets, with a distinct developmental plan for gamete synthesis which is regulated by integration of homeostatic inputs such as nutrient status, and environmental cues. Signaling pathways integrate and transduce information from these cues to evoke a response. A decline in homeostasis and subsequent cues occurs over time, in the case of reproductive tissues leading to a progressive loss of fertility. The Janus Kinase and …

The Encyclopedia Of North American Drosophilids Volume 1: Drosophilids Of The Midwest And Northeast, Thomas Werner, Tessa Steenwinkel, John Jaenike

Open Access Books

The Encyclopedia of North American Drosophilids: Volume 1: Drosophilids of the Midwest and Northeast provides an introduction to the flies of the family Drosophilidae of the Midwest and Northeast of the United States, as well as nearby regions in Canada. The book strives to facilitate identification of most of the drosophilid species in this region and provides remarks on interesting aspects of their biology and suggestions for future research on them. The book is intended for researchers, teachers, and students wishing to discover the diversity of these flies.

Version 4 is a major update that covers new species and includes …

Comparative Phylogeography, Taxonomy, And Neuroanatomy Of Montane Chameleons In The Albertine Rift, Central Africa, Daniel Hughes

Open Access Theses & Dissertations

How do traits vary across the tree of life? Our ability to address this question is diminished if: A taxonomic group has a poorly sampled phylogeny, a species goes extinct before their systematic position is resolved, or a trait is inadequately characterized for detailed studies. In the current era of mass extinction, it is imperative to not only accelerate species discovery through traditional studies in taxonomy and expeditionary research, but also to increase rescue efforts for all types of data before poorly understood species and potentially undescribed traits are lost. Here, an integrative taxonomic approach was used and novel methods …

Pitx1 Regulates Cement Gland Development In Xenopus Laevis Through Activation Of Transcriptional Targets And Inhibition Of Bmp Signaling, Ye Jin, Daniel C. Weinstein

Publications and Research

The cement gland in Xenopus laevis has long been used as a model to study the interplay of cell signaling and transcription factors during embryogenesis. It has been shown that an intermediate level of Bone Morphogenetic Protein (BMP) signaling is essential for cement gland formation. In addition, several transcription factors have been linked to cement gland development. One of these, the homeodomain-containing protein Pitx1, can generate ectopic cement gland formation; however, the mechanisms underlying this process remain obscure. We report here, for the first time, a requirement for Pitx proteins in cement gland formation, in vivo: knockdown of both pitx1 …

Elucidating The Role Of Nidogen In The Fusion Of The Choroid Fissure, Nicholas W. Carrara

Theses and Dissertations--Biology

In the developing embryo, the timely fusion of opposing epithelial sheets into one uniform layer denotes the completion of several developmental events. Failure of this epithelial sheet fusion event (ESF) within the choroid fissure (CF) is associated with the congenital disorder Ocular Coloboma, and is one of the leading causes of pediatric blindness. A requirement for a highly coordinated dismantling of the basement membrane (BM) to allow for fusion to occur is undoubted, however the underlying mechanisms of this process are poorly understood. Due to its BM crosslinking capabilities, I have hypothesized that the regulation of nidogen plays a crucial …

Wnt Secretion Proteins Modulate Rankl-Induced Expression Of Aire In Thymic Epithelial Cells, Daniel Pollack

Dissertations and Theses

Thymic epithelial cells (TEC) are essential for a proper adaptive immune response by regulating thymocyte development and establishing central tolerance. In the thymus, TECs differentially express Wnt proteins, which activate canonical and non-canonical Wnt signaling pathways. Wnt signaling is thought to regulate cell survival, proliferation, and development although the direct molecular mechanisms in TECs have yet to be elucidated. The inducible inhibition of canonical Wnt signaling with Dkk1 leads to a rapid loss of TEC progenitors as well as a decline in mature Aire-expressing mTECs. Therefore, we explore the role of Wnt ligands potentially responsible for stimulating and/or regulating Wnt …

Bone Marrow Derived Progenitor Cells And Their Contributions To The Thymic Stroma, Mohammed Hoque

Dissertations and Theses

The thymus serves as the primary lymphoid organ responsible for the development and selection of a self-tolerant T cell repertoire. In paradox to its critical functions for the adaptive immune response, the thymus undergoes a profound age associated decline beginning in early adult life resulting in significant decline in T-cell function.Thymic epithelial cells (TECs) are the most critical component of the thymic microenvironment and undergo rapid turn-over, so understanding the cellular mechanisms responsible for the maintenance of TEC number and organization will be critical in counteracting age associated involution, particularly in cancer patients, due to enhanced degeneration in response to …

Appropriate Preconditioning Of The Uterine Endoplasmic Reticulum Stress Response Inhibits Preterm Labor, Judith Ann Ingles

Wayne State University Dissertations

Introduction: In this study, we are testing the overarching hypothesis that preconditioning the myometrial UPR allows for the maintenance of non-apoptotic CASP3 activity and thus sustains uterine quiescence. We have previously demonstrated that the pregnant uterus facilitates uterine quiescence through UPR mediated activation of non-apoptotic CASP3, yet the mechanism in which CASP3 utilizes to avoid its apoptotic cell fate is unresolved. There is a growing body of evidence including our own that demonstrates remote and direct preconditioning with minor stresses propagates cytoprotective mechanisms that allow for the avoidance of apoptotic cell death upon exposure to a subsequent more damaging stress, …

Using The Frog Epidermis To Uncover Desmosome Function And Regulation In The Developing Embryo, Navaneetha Krishnan Bharathan

Theses and Dissertations

The desmosome is one of the major cell adhesion junctions found in the epithelia, heart, and hair follicle. Described as a “rivet” that hold cells together, it provides these tissues with the integrity to withstand the tremendous forces they face in everyday life. Defects in this junction can lead to devastating diseases where patients are susceptible to skin infections and cardiovascular defects. Limited treatments exist for diseases of the desmosome, and strategies do not target all symptoms. Therefore, delineating the function and regulation of desmosomes is of paramount importance for the development of prevention and treatment strategies. The Xenopus laevis …

Chromodomain Helicase Dna Binding Protein 1 (Chd1) Is Required For Orofacial Development In Xenopus, Brent Wyatt

Theses and Dissertations

Abnormalities affecting orofacial development are some of the most common, expensive, and devastating birth defects. Children born with such defects may experience difficulties with eating, breathing, and speech and in addition, these defects often require multiple surgeries to correct them. Therefore, it is critical to understand how the orofacial region develops in order to better treat and prevent these types of birth defects. Xenopus laevis has emerged as a strong model in which to examine orofacial development and was utilized here to investigate the cellular and molecular mechanisms underlying the complex development of the orofacial region. Retinoic acid is one …

Stat3 In The Regulation Of Brown Adipocyte Differentiation, Marc Cantwell

Theses and Dissertations

Thermogenic fat is a promising target for new therapies in diabetes and obesity. Understanding how thermogenic fat develops is important to develop rational strategies to treat obesity. Previously, we have shown that Tyk2 and STAT3, part of the JAK-STAT pathway, are necessary for proper development of classical brown fat. Using primary preadipocytes isolated from newborn mice we demonstrate that STAT3 is required for differentiation and robust expression of Uncoupling Protein 1. We also confirm that STAT3 is necessary during the early induction stage of differentiation and is dispensable during the later terminal differentiation stage. Without STAT3, the brown preadipocytes have …

Comparative Study Of Spinning Field Development In Two Species Of Araneophagic Spiders (Araneae, Mimetidae, Australomimetus), Mark A. Townley, Danilo Harms

Molecular, Cellular & Biomedical Sciences

External studies of spider spinning fields allow us to make inferences about internal silk gland biology, including what happens to silk glands when the spider molts. Such studies often focus on adults, but juveniles can provide additional insight on spinning apparatus development and character polarity. Here we document and describe spinning fields at all stadia in two species of pirate spider (Mimetidae: Australomimetus spinosus, A. djuka). Pirate spiders nest within the ecribellate orb-building spiders (Araneoidea), but are vagrant, araneophagic members that do not build prey-capture webs. Correspondingly, they lack aggregate and flagelliform silk glands (AG, FL), specialized for forming prey-capture …

Mechanics Of The Developing Brain: From Smooth-Walled Tube To The Folded Cortex, Kara Ellspermann Garcia

McKelvey School of Engineering Graduate Student Theses & Dissertations

Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.

First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for …

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity …

Transcriptome Profiling Of Cleft Palate Intgf-Beta3 Knockout Mice Alleles: Rna-Seq Analysis Of Tgf-Beta3 Mice, Kelsey White

Theses & Dissertations

Background: Orofacial clefts are the most common craniofacial birth defect with a complex, combinatorial etiology. Tgf-b3 regulates palatal fusion in mice; Tgf-b3 knockout mice have cleft palate (CP) lacking other major deformities. The genes downstream of Tgf-b3 during palatogenesis remain largely unexplored. Our objective was to analyze the global transcriptome changes and their contribution to CP and identify novel Tgf-b3 associated genes involved in formation of CP. We used RNA-sequencing to analyze and compare the whole transcriptome of Tgf-b3 alleles during palatal growth and fusion in mice.

Results: …

Establishment Of Lateral Organ Asymmetries In The Invertebrate Chordate, Ciona Intestinalis, Karl Palmquist , '17, Bradley Justin Davidson , '91

Biology Faculty Works

Background: The evolutionary emergence and diversification of the chordates appear to involve dramatic changes in organ morphogenesis along the left/right axis. However, the ancestral chordate mechanism for establishing lateral asymmetry remains ambiguous. Additionally, links between the initial establishment of lateral asymmetry and subsequent asymmetries in organ morphogenesis are poorly characterized. Results: To explore asymmetric organ morphogenesis during chordate evolution, we have begun to characterize left/right patterning of the heart and endodermal organs in an invertebrate chordate, Ciona intestinalis. Here, we show that Ciona has a laterally asymmetric, right-sided heart. Our data indicate that cardiac lateral asymmetry requires H+/K+ ion flux, …

Identifying Genetic Factors Influencing Sperm Mobility Phenotype In Chicken Using Genome Wide Association Studies, Primordial Germ Cell Transplantation, And Rnaseq., Sohita Ojha

Graduate Theses and Dissertations

Sperm mobility is a major determinant of male fertility in chicken. In spite of low heritability of reproductive traits, sperm mobility has high heritability index which suggests presence of quantitative trait loci (QTLs) governing the trait. Our research focused on three objectives: i) to identify the QTLs affecting low mobility phenotype in chicken, ii) to understand the impact of Sertoli-cells and germ cells interactions in influencing the mobility phenotype and iii) to identify the genes and gene networks differentially expressed in male and female PGCs. To detect the QTLs, genome wide association studies (GWAS) was conducted which revealed the presence …

Butyl Benzyl Phthalate (Bbp) Induces Caudal Defects During Embryonic Development, Nicole M. Roy, Ewelina Zambrzycka, Jenna Santangelo

Biology Faculty Publications

Butyl benzyl phthalate (BBP) is commonly added during the manufacturing of plastics to increase flexibility and elasticity. However, BBP leaches off of plastic and environment presence has been detected in soil, groundwater and sediment potentially effecting organisms in the environment. Given the widespread uses of BBP in household, consumer goods and the presence of BBP in the environment, studies on developmental toxicity are needed. Here, we use a zebrafish model to investigate the early developmental toxicity of BBP. We treated gastrula staged embryos with increasing concentrations of BBP and noted concentration-dependent defects in caudal tail development, but the effect was …

Pam-1 Localizations In The Regulation Of Autophagy During Caenorhabditis Elegans Oogenesis, Ashley N. Munie

Steeplechase: An ORCA Student Journal

Autophagy, the cell's recycling system, is a highly-conserved survival mechanism of the cell. Autophagy has been implicated in the mediation of the removal of cytotoxic aggregates, such as those linked to neurodegenerative disorders like Huntington and Alzheimer disease. Studies in several model organisms have identified numerous genes involved in mediating autophagy, including the Puromycin sensitive aminopeptidase (Psa). The Caenorhabditis elegans orthologue of Psa, pam-1, also governs fertility. Along with apoptosis, a form of regulated cell death, autophagy has been found to be required for efficient C. elegans oogenesis. When autophagy is suppressed through RNAi in worms harboring …

An Undergraduate Laboratory Manual For Analyzing A Crispr Mutant With A Predicted Role In Regeneration, Susan Walsh, Ashley Becker, Paxton S. Sickler, Damian G. Clarke, Erin Jimenez

Faculty Publications

Exposing students to undergraduate research has reportedly improved students’ development of knowledge and skills in the laboratory, self-efficacy, satisfaction with their research, retention, and perseverance when faced with obstacles. Furthermore, utilizing authentic course-based undergraduate research experiences (CUREs) includes all students enrolled in the class, giving those who may not otherwise have access to an independent undergraduate research project an opportunity to engage in the scientific process in context of an original, unanswered question. In the fall of 2016, second semester introductory biology students conducted a semester-long research project on the transcription factor Lin28a to determine the effect of Lin28a on …

Optimizing Sperm Collection Procedures In Zebrafish, Madelyn B. Wasden, Rachel L. Roberts, April Delaurier

Journal of the South Carolina Academy of Science

Zebrafish are a highly-valued model organism used for developmental biology research. Zebrafish can be used for genetic manipulation and hence, many mutant and transgenic lines exist. It is impractical to maintain lines of adult zebrafish, due to resource constraints and the need to continuously produce new generations. Therefore, a practical way to preserve zebrafish lines is to freeze sperm and retrieve lines using in vitro fertilization of fresh eggs. Most existing in vitro protocols used by research labs have a wide variety of fertilization rates (ranging from 0% to >90%). Due to this variability, lines may be at risk of …

The Evolutionary Origin Of Digit Patterning, T Stewart, Ramray Bhat, Stuart Newman

NYMC Faculty Publications

The evolution of tetrapod limbs from paired fins has long been of interest to both evolutionary and developmental biologists. Several recent investigative tracks have converged to restructure hypotheses in this area. First, there is now general agreement that the limb skeleton is patterned by one or more Turing-type reaction-diffusion, or reaction-diffusion-adhesion, mechanism that involves the dynamical breaking of spatial symmetry. Second, experimental studies in finned vertebrates, such as catshark and zebrafish, have disclosed unexpected correspondence between the development of digits and the development of both the endoskeleton and the dermal skeleton of fins. Finally, detailed mathematical models in conjunction with …

Primary Cilium-Dependent Signaling Mechanisms, Rajasekharreddy Pala, Nedaa Alomari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like organelles and play crucial roles in vertebrate development, organogenesis, health, and many genetic disorders. A primary cilium is a mechano-sensory organelle that responds to mechanical stimuli in the micro-environment. A cilium is also a chemosensor that senses chemical signals surrounding a cell. The overall function of a cilium is therefore to act as a communication hub to transfer extracellular signals into intracellular responses. Although intracellular calcium has been one of the most studied signaling messengers that transmit extracellular signals into the cells, calcium signaling by various ion channels remains a topic of interest in the field. …