Genetic Regulation Of Caenorhabditis Elegans Post Embryonic Development Involving The Transcription Factors Egl 38 Vab 3 And Lin 14

Abstract: Sequence-specific transcription factors are crucial to generating the gene expression patterns that drive the specification, morphogenesis, and physiology of organs and tissues. In order to better understand how organ form and function are orchestrated by transcription factors, we must better understand the genetic inputs and outputs of these critical regulators. In this work, I have utilized C. elegans to characterize the genetic networks and organ functions of three post-embryonically functioning transcription factors. The Pax family of transcription factors is highly conserved across animal species, and controls the development of multiple tissues and organs during development. In C. elegans males, two sensory mating structures, the copulatory spicules and the post-cloacal sensilla, are formed from stereotyped divisions of the two post-embryonic blast cells, B.a and Y.p, respectively. A C. elegans pax-6 transcript, vab-3, is necessary for the development of these sensory structures. Using a green fluorescent protein (GFP)-based vab-3 transcriptional reporter, I found that expression is restricted to the sensory organ lineages of B.a and Y.p. Transcription of vab-3 in the tail region of the worm requires the Abdominal-B homeobox gene, egl-5. Opposing this activation, a transcription factor cascade and a Wnt signaling pathway each act to restrict vab-3 expression to the appropriate cell lineages. Another C. elegans Pax gene, egl-38, is required for the development of the egg-laying system and rectum. However, few EGL-38 target genes are known. Using gene expression microarrays, we cross-referenced microarray data from an inducible EGL-38 strain and two egl-38 mutants that disrupt protein function in a tissue-preferential manner to identify potential tissue-specific EGL-38 target genes. One set of genes from this analysis was validated using GFP reporter transgenes. Most of these genes are expressed in egl-38-dependent tissues, and many display egl-38 dependence. In addition to the identification of target genes, this work revealed enrichments in gene classes that play a role in innate immunity. Consistent with this, we discovered a novel immune function for egl-38. We found that the gene activities of egl-38 and three egl-38-responsive genes from our validation set are associated with increased infection by the pathogenic bacterium M. nematophilum. However, we also show that egl-38 does not impact infection by a different pathogen, S. marcescens. While Pax genes regulate spatial tissue/organ identity, some transcription factors regulate temporal identity. In C. elegans, heterochronic genes function to ensure the precise timing of stage-specific developmental events. I positionally cloned a novel missense allele of the heterochronic transcription factor LIN-14, and revealed a previously undiscovered ability of this protein to solely affect late larval development. lin-14(sa485) hermaphrodites exhibit asynchrony between vulval and gonadal morphogenesis and maturation. Further, lin-14(sa485) preferentially disrupts the timing of vulval cell morphogenesis, but not cell division. I also show that terminal differentiation of a uterine cell type is delayed in lin-14(sa485) mutants.

Finally, I extended my analysis to the C. elegans MEIS homolog unc-62, because this family of homeodomain proteins participate in the DNA bound complexes of Hox or Hox-PBC. Lacking unc-62 activity causes "loss of M lineage descendants" phenotypes as seen in ceh-20 or hox mutants. I also provide genetic evidence that UNC-62 may function in a Hox-CEH-20 complex to regulate hlh-8 expression and promote multiple cell fates in the M lineage. In addition to their genetic interaction, CEH-20 and UNC-62 display mutual regulatory interactions by regulating each others expression.

egl-38(n578) mutant animals exhibit of high levels of Programmed Cell Death (PCD) in the germline and the soma. Wild-type EGL-38 can transcriptionally regulate the bcl-2 gene, ced-9 in C. elegans. In this dissertation, I performed mosaic analysis for EGL-38 and found that its activity is required in both the germline and soma to promote germline cell survival.

Defines the current status of research in the genetics, anatomy, and development of the nematode C. elegans, providing a detailed molecular explanation of how development is regulated and how the nervous system specifies varied aspects of behavior. Contains sections on the genome, development, neural networks and behavior, and life history and evolution. Appendices offer genetic nomenclature, a list of laboratory strain and allele designations, skeleton genetic maps, a list of characterized genes, a table of neurotransmitter assignments for specific neurons, and information on codon usage. Includes bandw photos. For researchers in worm studies, as well as the wider community of researchers in cell and molecular biology. Annotation copyrighted by Book News, Inc., Portland, OR

All animals, including humans, derive from a single cell, which possesses all the genetic instructions needed to define how the animal will look like. However, during development, the millions of cells that derive from the zygote will only select part of this genetic information to give rise to the various organs of the body. The coordination of different cell behaviours during development results in the formation of specialized tissues and organs giving rise to highly adapted animals. This book provides an overview of how this diversification is achieved during organ formation and how it may have evolved. Conserved cellular processes are presented using examples from selected vertebrate and invertebrate species that illustrate how developmental biologists are solving the complex puzzle of organ formation. This volume is aimed to students, researchers and medical doctors alike who want to find a simple but rigorous introduction on how gene networks control organ formation.“div> /div

This book devotes a chapter to each RTK family and the multiple receptors within each family, thoroughly covering all of the RTKs. The chapters all follow the same structure, presenting this essential information in an accessible and user-friendly format. Each chapter covers one specific family of receptors and begins with a general introduction to that family and a comprehensive discussion of that receptor’s family in development and human disease. Following are in-depth analyses of each family’s receptors with discussions on the gene, protein, ligands, activation, and signaling pathways along with discussion of receptor processing and signal attenuation. Further, cross talk with other receptors systems, post-translational modification and specific unique characteristics to each RTK are discussed. Because it isolates and explains each family, this book is an essential companion volume to Receptor Tyrosine Kinases: Structure, Functions and Role in Human Disease, by the same authors, which talks about RTKs more generally and without the family-by-family detail.

This book will focus on the molecular basis of oxidative stress induced by toxicants or stresses and various molecular signalling pathways in regulating the toxicity of toxicants or stresses in Caenorhabditis elegans. It will also cover the discussion on the aspects of response signals, G-protein coupled receptors and ion channels, specific molecular signals, and epigenetic signals involved in the regulation of toxicity from toxicants or stresses. The molecular basis for adaptive response for transgenerational toxicity of environmental toxicants or stresses will be further discussed. Nematode Caenorhabditis elegans is a classic model animal with well-described genetic and developmental backgrounds based on the study of life science, and has been further successfully and widely used in both toxicity assessment and toxicological study of various environmental toxicants or stresses. Based on related available data, this book aims at providing a systematic understanding of the knowledge system of molecular toxicology in C. elegans.

The first of its kind, this laboratory handbook emphasizes diverse methods and technologies needed to investigate C. elegans, both as an integrated organism and as a model system for research inquiries in cell, developmental, and molecular biology, as well as in genetics and pharmacology. Four primary sections--Genetic and Culture Methods, Neurobiology, Cell and Molecular Biology, and Genomics and Informatics--reflect the cross-disciplinary nature of C. elegans research. Because C. elegans is a simple and malleable organism with a small genome and few cell types, it provides an elegant demonstr.