Developmental Biology Commons^™

Evolutionary Genomics And Adaptive Evolution Of The Hedgehog Gene Family (Shh, Ihh And Dhh) In Vertebrates, Joana Pereira, Warren E. Johnson, Stephen J. O'Brien, Erich D. Jarvis, Guojie Zhang, M. Thomas P. Gilbert, Vitor Vasconcelos, Agostinho Antunes

Biology Faculty Articles

The Hedgehog (Hh) gene family codes for a class of secreted proteins composed of two active domains that act as signalling molecules during embryo development, namely for the development of the nervous and skeletal systems and the formation of the testis cord. While only one Hh gene is found typically in invertebrate genomes, most vertebrates species have three (Sonic hedgehog – Shh; Indian hedgehog – Ihh; and Desert hedgehog – Dhh), each with different expression patterns and functions, which likely helped promote the increasing complexity of vertebrates and their successful diversification. In this study, we …

Ontogenetic Scaling Patterns And Functional Anatomy Of The Pelvic Limb Musculature In Emus (Dromaius Novaehollandiae), Luis P. Lamas, Russell P. Main, John R. Hutchinson

Department of Basic Medical Sciences Faculty Publications

Emus (Dromaius novaehollandiae) are exclusively terrestrial, bipedal and cursorial ratites with some similar biomechanical characteristics to humans. Their growth rates are impressive, as their body mass increases eighty-fold from hatching to adulthood whilst maintaining the same mode of locomotion throughout life. These ontogenetic characteristics stimulate biomechanical questions about the strategies that allow emus to cope with their rapid growth and locomotion, which can be partly addressed via scaling (allometric) analysis of morphology. In this study we have collected pelvic limb anatomical data (muscle architecture, tendon length, tendon mass and bone lengths) and calculated muscle physiological cross sectional area …

Subcellular Metabolite And Lipid Analysis Of Xenopus Laevis Eggs By Laesi Mass Spectrometry, Bindesh Shrestha, Prabhakar Sripadi, Brent R. Reschke, Holly D. Henderson, Matthew J. Powell, Sally Ann Moody, Akos Vertes

Anatomy and Regenerative Biology Faculty Publications

Xenopus laevis eggs are used as a biological model system for studying fertilization and early embryonic development in vertebrates. Most methods used for their molecular analysis require elaborate sample preparation including separate protocols for the water soluble and lipid components. In this study, laser ablation electrospray ionization (LAESI), an ambient ionization technique, was used for direct mass spectrometric analysis of X. laevis eggs and early stage embryos up to five cleavage cycles. Single unfertilized and fertilized eggs, their animal and vegetal poles, and embryos through the 32-cell stage were analyzed. Fifty two small metabolite ions, including glutathione, GABA and amino …

Arabidopsis Chromatin Remodeler Brahma: Its Functional Interplay With Polycomb Proteins And The Ref6 Histone Demethylase, Chenlong Li

Electronic Thesis and Dissertation Repository

BRAHMA (BRM) is a SWI/SNF-type chromatin remodeling ATPase that plays an important role in regulation of gene expression. Tri-methylation of lysine 27 on histone H3 (H3K27me3) is a histone modification that is associated with transcriptionally repressed genes and catalyzed by Polycomb Group (PcG) proteins. BRM has been proposed to antagonize the function of PcG proteins but the underlying molecular mechanism is unclear. To understand how BRM regulates the function of PcG proteins during plant development, a genome-wide analysis of H3K27me3 in brm mutant was performed using chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Loss of BRM leads to increased …

The Drosophila T-Box Transcription Factor Midline Functions Within The Insulin/Akt And C-Jun-N-Terminal Kinase Signaling Pathways To Regulate Interomatidial Bristle Formation And Cell Survival, Qichuan Chen

Master's Theses

From a genetic and allelic modifier screen, we report that the Drosophila melanogaster T-box transcription factor midline (mid), a homolog to the human TBX20 gene, interacts with dFOXO within the insulin receptor (InR) and the c-Jun-N-terminal kinase (JNK) signaling pathways to regulate interommatidial bristle (IOB) formation. Previous studies have identified mid’s role in cell fate specification of sensory organ precursor cells in conjunction with the Notch-Delta signaling pathway (Das et al., 2013). The Notch, InR, and JNK signaling pathways regulate dFOXO activity under conditions of stress. Thus, we determined the effects of oxidative stress and metabolic stress by …

Sox2-Dependent Transcriptional Control Of Airway Differentiation In The Mouse Lung, Belinda J. Hernandez

Dissertations & Theses (Open Access)

The lung is a highly branched tree-like tubular system that results from more than 20 generations of the conducting airways and consists of 300 million alveoli for gas exchange. Airway branches form via branching morphogenesis and then mature into conducting airways, in which the number and distribution of different cell types need to be precisely controlled. The conducting airways contain four lung cell types: club cells, ciliated cells, basal cells, and neuroendocrine cells.SOX2 is a well-known conducting airway marker. SOX2 is a transcription factor that is known to be important in embryonic development and induction of pluripotent stem cells. We …

P120-Catenin Regulates Rest And Corest, And Modulates Mouse Embryonic Stem Cell Differentiation, Moonsup Lee

Dissertations & Theses (Open Access)

The canonical-Wnt pathway and beta-catenin have been extensively studied to determine their contributions to stem cell biology, but less is known about p120-catenin in the nuclear compartment. P120 is developmentally required as a consequence of its biochemical and functional interactions with cadherins, small-GTPases and transcriptional regulators. We report here that p120-catenin binds to and negatively regulates REST and CoREST, that others have indicated form a repressive complex having diverse key roles in developmental and pathologic gene regulation. We thus provide the first evidence for a direct upstream modulator of REST/CoREST function. Using mouse embryonic stem cells (mESCs), mammalian cell lines, …

Characterization Of Ca2+ Influx Pathway(S) During Mouse Oocyte Maturation, Banyoon Cheon

Doctoral Dissertations

Ca²⁺ signaling induced at fertilization, also known as oscillations, is essential in mammalian eggs to initiate early embryonic development. The generation of the oscillations relies on optimization of Ca²⁺ toolkit components during oocyte maturation. In this dissertation, we intend to deepen our understanding of how this differentiation of the Ca²⁺ toolkit, especially those components associated with Ca²⁺ influx, is achieved during maturation, and how it contributes to the filling of the ER Ca²⁺ store during the maturation and fertilization. We first identified the expression and characterized the function of the components of the Store Operated …

Asynchronous Remodeling Is A Driver Of Failed Regeneration In Duchenne Muscular Dystrophy, Sherry Dadgar, Zuyi Wang, Helen Johnston, Akanchha Kesari, Kanneboyina Nagaraju, Yi-Wen Chen, D. Ashley Hill, Terence A. Partridge, Robert J. Freishtat, Javad Nazarian, Jianhua Xuan, Yue Wang, Eric P. Hoffman

Genomics and Precision Medicine Faculty Publications

We sought to determine the mechanisms underlying failure of muscle regeneration that is observed in dystrophic muscle through hypothesis generation using muscle profiling data (human dystrophy and murine regeneration). We found that transforming growth factor β-centered networks strongly associated with pathological fibrosis and failed regeneration were also induced during normal regeneration but at distinct time points. We hypothesized that asynchronously regenerating microenvironments are an underlying driver of fibrosis and failed regeneration. We validated this hypothesis using an experimental model of focal asynchronous bouts of muscle regeneration in wild-type (WT) mice. A chronic inflammatory state and reduced mitochondrial oxidative capacity are …

Neural Transcription Factors: From Embryos To Neural Stem Cells, Hyun-Kyung Lee, Hyun-Shik Lee, Sally Ann Moody

Anatomy and Regenerative Biology Faculty Publications

The early steps of neural development in the vertebrate embryo are regulated by sets of transcription factors that control the induction of proliferative, pluripotent neural precursors, the expansion of neural plate stem cells, and their transition to differentiating neural progenitors. These early events are critical for producing a pool of multipotent cells capable of giving rise to the multitude of neurons and glia that form the central nervous system. In this review we summarize findings from gain- and loss-of-function studies in embryos that detail the gene regulatory network responsible for these early events. We discuss whether this information is likely …

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster., Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …

Tbx5 Is Required For Avian And Mammalian Epicardial Formation And Coronary Vasculogenesis., Nata Y Diman, Gabriel Brooks, Boudewijn P Kruithof, Olivier Elemento, Jonathan G Seidman, Christine Seidman, Craig T Basson, Cathy J. Hatcher

PCOM Scholarly Papers

Rationale: Holt-Oram syndrome (HOS) is an autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. Overexpression of Tbx5 in the chick proepicardial organ (PEO) impaired coronary blood vessel formation. However, the potential activity of Tbx5 in the epicardium itself, and Tbx5's role in mammalian coronary vasculogenesis, remains largely unknown. Objective: To evaluate the consequences of altered Tbx5 gene dosage during PEO and epicardial development in the embryonic chick and mouse. Methods and Results: Retroviral-mediated knockdown or upregulation of Tbx5 expression in the embryonic chick PEO as well as proepicardial-specific deletion of Tbx5 in the embryonic mouse (Tbx5(epi-/-)) impaired …

Pregestational Diabetes And Congenital Heart Defects: Role Of Reactive Oxygen Species, Hoda Moazzen

Electronic Thesis and Dissertation Repository

Women with pregestational diabetes are at a high risk of having babies with congenital heart defects (CHDs). The mechanisms of CHD induction in the offspring of women with pregestational diabetes remain elusive. With an ever-increasing rate of diabetes in young adults, there is a pressing need to understand the underlying mechanisms and initiate effective preventative strategies. The aim of this thesis is to study the role of reactive oxygen species (ROS) signalling in heart morphogenesis, unravel molecular mechanisms of CHDs induced by pregestational diabetes and provide new insights on potential therapeutic strategies. To this end, a mouse model of pregestational …

Measurement Of Mullerian Inhibiting Substance Facilitates Management Of Boys With Microphallus And Cryptorchidism, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a gonadal hormone expressed in a sexually dimorphic pattern. In males, serum MIS reflects Sertoli cell function and provides an estimate of seminiferous tubular integrity. We examined the role of MIS determination in the evaluation of boys with microphallus (n = 62) and/or cryptorchidism (n = 156). MIS was normal in 69.2% of boys with isolated microphallus compared with 38.1% of boys with microphallus and coexisting cryptorchidism (P < 0.05). In the cryptorchid group, MIS was normal in 46.8%, low in 24.4%, and absent in 28.8%. Normal values for age were associated with testicular tissue, whereas …

Augmented Growth Hormone (Gh) Secretory Burst Frequency And Amplitude Mediate Enhanced Gh Secretion During A Two-Day Fast In Normal Men, Mark Hartman, Johannes Veldhuis, Michael Johnson, Mary Lee, K. Alberti, Eugene Samojlik, Michael Thorner

Mary M. Lee

Serum GH concentrations are increased in fasted or malnourished human subjects. We investigated the dynamic mechanisms underlying this phenomenon in nine normal men by analyzing serum GH concentrations measured in blood obtained at 5-min intervals over 24 h on a control (fed) day and on the second day of a fast with a multiple-parameter deconvolution method to simultaneously resolve endogenous GH secretory and clearance rates. Two days of fasting induced a 5-fold increase in the 24-h endogenous GH production rate [78 +/- 12 vs. 371 +/- 57 micrograms/Lv (Lv, liter of distribution volume) or 0.24 +/- 0.038 vs. 1.1 +/- …

Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe

Mary M. Lee

We have isolated a candidate Mullerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Mullerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II …

Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck

Mary M. Lee

Mullerian inhibiting substance (MIS) is a 140-kilodalton homodimeric glycoprotein that causes regression of the Mullerian ducts in male embryos, and may also have a role in both males and females in the regulation of germ cell maturation. We examined the ontogeny of MIS messenger RNA (mRNA) in rat testes from midgestation through adulthood and found two discrete MIS mRNA species that are developmentally regulated. The larger 2.0-kilobase species is abundant at embryonic day 14, then decreases in late gestation, and is barely detectable after birth. The smaller 1.8-kilobase species is first noted at embryonic day 18 and is the major …

Transient Hyperthyroidism In An Adolescent With Hydatidiform Mole, Madhusmita Misra, Lynne Levitsky, Mary Lee

Mary M. Lee

No abstract provided.

Mullerian Inhibiting Substance In Humans: Normal Levels From Infancy To Adulthood, Mary Lee, Patricia Donahoe, Tomonobu Hasegawa, Bernard Silverman, Gretchen Crist, Sharon Best, Yukihiro Hasegawa, Richard Noto, David Schoenfeld, David Maclaughlin

Mary M. Lee

Mullerian-inhibiting substance (MIS) is a gonadal hormone synthesized by Sertoli cells of the testis and granulosa cells of the ovary. To facilitate the use of MIS for the evaluation of intersex disorders and as a tumor marker in women with MIS-expressing ovarian tumors, we measured MIS in 600 serum samples from males and females. These data show that mean MIS values for males rise rapidly during the first year of life and are highest during late infancy, then gradually decline until puberty. In contrast, MIS values in females are lowest at birth and exhibit a minimal increase throughout the prepubertal …

Serum Concentrations Of Organochlorine Pesticides And Growth Among Russian Boys, Jane Burns, Paige Williams, Oleg Sergeyev, Susan Korrick, Mary Lee, Boris Revich, Larisa Altshul, Julie Del Prato, Olivier Humblet, Donald Patterson, Wayman Turner, Mikhail Starovoytov, Russ Hauser

Mary M. Lee

BACKGROUND: Limited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth. OBJECTIVE: We evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels. METHODS: A cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and …

Mullerian Inhibiting Substance In The Diagnosis And Management Of Intersex And Gonadal Abnormalities, Michael Gustafson, Mary Lee, Lara Asmundson, David Maclaughlin, Patricia Donahoe

Mary M. Lee

Mullerian inhibiting substance (MIS), a gonadal hormone important in sexual differentiation, is high (10 to 70 ng/mL) in human male serum postnatally for several years before declining during the peripubertal period, but is undetectable in female serum until the onset of puberty. The sexually dimorphic secretion of MIS suggested possibilities for its use in several clinical settings. Thirty-one patients with intersex and gonadal anomalies from 17 institutions were therefore evaluated between 1989 and 1992 with an MIS enzyme-linked immunosorbent assay (ELISA). Serum MIS levels correlated with the presence of testicular tissue in two patients with suspected anorchia, five patients with …

Campylobacter Meningitis In Childhood, Mary Lee, Robert Welliver, Leonard La Scolea

Mary M. Lee

No abstract provided.

Mentoring Fathers Of Children Newly Diagnosed With T1dm, Susan Sullivan-Bolyai, Carol Bova, Mary Lee, Philip Gruppuso

Mary M. Lee

PURPOSE: To pilot test a social support intervention for fathers of children (T1DM).

DESIGN AND METHODS: The pilot study was part of a larger randomized, controlled clinical trial. Father participants (28 fathers of children newly diagnosed) were recruited from two pediatric diabetes centers. For 12 months fathers (n = 19) and their spouses in the experimental arm received social support (home visits and phone calls). Control group fathers (n = 9) and their spouses received the phone number of an experienced parent (but not formally educated to provide social support) to call as needed.

RESULTS: Fathers in the intervention group …

The Role Of Mullerian Inhibiting Substance In The Evaluation Of Phenotypic Female Patients With Mild Degrees Of Virilization, Madhusmita Misra, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a sexually dimorphic gonadal hormone with proven efficacy in the evaluation of boys with cryptorchidism and children with intersex conditions. We examined the role of MIS determination in the evaluation of 65 phenotypic females with mild virilization. Among the 28 subjects with MIS values elevated above the normal female range, all had abnormal gonadal tissue: ovotestes in 11, testes in 7, dysgenetic gonads in 7, and MIS-secreting ovarian tumors in 3. Among the 37 children with serum MIS in the normal female range, 19 had detectable MIS and 18 had unmeasurable MIS. In the former …

Alterations In The Pulsatile Mode Of Growth Hormone Release In Men And Women With Insulin-Dependent Diabetes Mellitus, Christopher Asplin, Amilton Faria, Elizabeth Carlsen, Veronica Vaccaro, Richard Barr, Ali Iranmanesh, Mary Lee, Johannes Veldhuis, William Evans

Mary M. Lee

The mechanisms responsible for the elevated levels of circulating GH observed in diabetes mellitus (DM) remain incompletely defined. To assess the episodic fluctuations in serum GH as a reflection of hypothalamic-pituitary activity, we accumulated GH concentration-time series in a total of 48 adult men and women with and without insulin-dependent DM by obtaining serum samples at 10-min intervals over 24 h. Significant pulses of GH release were subsequently identified and characterized by an objective, statistically based pulse detection algorithm (Cluster) and fixed circadian (24-h) periodicities of secretory activity, resolved using Fourier expansion timeseries analysis. Compared to those in age-matched controls, …

Hypothyroidism In Down Syndrome: Screening Guidelines And Testing Methodology, Olga Hardy, Gordon Worley, Mary Lee, Shu Chaing, Joanne Mackey, Blythe Crissman, Priya Kishnani

Mary M. Lee

No abstract provided.

Mullerian Inhibiting Substance As A Marker For Ovarian Sex-Cord Tumor, Michael Gustafson, Mary Lee, Robert Scully, Ashby Moncure, Toshio Hirakawa, Annekathryn Goodman, Howard Muntz, Patricia Donahoe, David Maclaughlin, Arlan Fuller

Mary M. Lee

No abstract provided.

Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered …

Mullerian Inhibiting Substance Is Present In Embryonic Testes Of Dogs With Persistent Mullerian Duct Syndrome, Vicki Meyers-Wallen, Mary Lee, T. Manganaro, T. Kuroda, David Maclaughlin, Patricia Donahoe

Mary M. Lee

Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian ducts during a critical period in embryonic development in male mammals. In Persistent Mullerian Duct Syndrome (PMDS), an autosomal recessive trait in humans and dogs, the Mullerian ducts fail to regress in otherwise normal males. Previously we reported that PMDS-affected dogs produce bioactive testicular MIS postnatally. The purpose of the present study was to determine whether PMDS-affected canine embryos appropriately express MIS mRNA and protein during the critical period for Mullerian duct regression. Homozygous (PMDS-affected) and normal canine embryos were removed from timed pregnancies. Gonadal sex and the degree of Mullerian …

Mis/Amh In The Assessment Of Cryptorchidism And Intersex Conditions, Mary Lee, Madhusmita Misra, Patricia Donahoe, David Maclaughlin

Mary M. Lee

Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH), causes Mullerian duct involution during male sexual differentiation and also has a postnatal regulatory role in the gonads. Serum MIS/AMH has a gonad specific pattern of expression and its concentrations are sexually dimorphic in children; hence measurement of serum MIS/AMH helps in the evaluation of children with gonadal disorders. In boys with cryptorchidism (non-palpable gonads), serum MIS/AMH correlates with testicular tissue. A measurable value is predictive of undescended testes while an undetectable value is highly suggestive of anorchia. In minimally virilized phenotypic females, MIS/AMH helps differentiate between gonadal and non-gonadal …