A Transcription Factor Network Required To Regulate Caenorhabditis Elegans Postembryonic Mesodermal Development

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.

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.

The fundamental question of developmental biology is how a single cell can generate a multicellular organism with a diverse set of cell types with specialized functions. A classic example of this paradigm is how the mesodermal germ layer of metazoan species can give rise to a range of cell types, including cells that form muscle, bone, blood, kidneys and the heart in vertebrate organisms. In my dissertation, I have used the C. elegans postembryonic mesoderm as a model to study the mechanisms of how various cell fates can be specified from the mesoderm. The C. elegans postembryonic mesoderm, or the M lineage, gives rise to a small, but diverse, set of cell types that include striated body wall muscles (BWMs), non-muscle cells of a scavanger-like function known as coelomocytes (CCs), and sex myoblasts (SMs), which further divide and generate the non-striated sex muscles used for egg-laying. My project began with the characterization of the gene fozi-1, which was identified in a screen for M lineage mutant phenotypes. fozi-1 encodes a unique transcription factor that functions autonomously in the M lineage for the proper specification of BWMs and CCs. Moreover, fozi-1 functions redundantly with the MyoD homolog hlh-1 and the Hox gene mab-5 to specify the myogenic BWM fate. In an RNAi screen to search for additional factors required for M lineage development, I identified 37 transcription factors that are required for proper M lineage development. I have focused my studies on one of these genes, ceh-34, which encodes a homeodomain protein that is conserved among metazoans. I found that CEH-34 and its cofactor EYA-1 are individually required for the CC fate and together can induce the specification of CC fates from cells that will normally become BWMs. I present evidence for the regulation of ceh-34 and eya-1 by the transcription factors fozi-1, hlh-1 and mab-5, along with well-conserved signaling mechanisms that regulate dorsal-ventral (TGF[beta] and Notch) and anterior-posterior (Wnt) asymmetry within the M lineage to specify non-muscle fates. Many of the components functioning in the M lineage are conserved in metazoans, and similar paradigms have also been found in Drosophila mesodermal fate specification, suggesting that the mechanism for distinguishing non-myogenic and myogenic fates in the mesoderm is conserved in other animals.

Connects classical cellular descriptive studies with more recent work on the molecular and genetic aspects regarding germline development. Prominent scientists discuss research on a range of organisms including insects, worms, birds, fish, amphibia, mammals and green algae. Specification of germ cells, their migration to the gonads and subsequent interactions with the soma and evolutionary factors of their segregation are among the topics covered.

The interaction between biology and evolution has been the subject of great interest in recent years. Because evolution is such a highly debated topic, a biologically oriented discussion will appeal not only to scientists and biologists but also to the interested lay person. This topic will always be a subject of controversy and therefore any breaking information regarding it is of great interest.The author is a recognized expert in the field of developmental biology and has been instrumental in elucidating the relationship between biology and evolution. The study of evolution is of interest to many different kinds of people and Genomic Regulatory Systems: In Development and Evolution is written at a level that is very easy to read and understand even for the nonscientist. * Contents Include* Regulatory Hardwiring: A Brief Overview of the Genomic Control Apparatus and Its Causal Role in Development and Evolution * Inside the Cis-Regulatory Module: Control Logic and How the Regulatory Environment Is Transduced into Spatial Patterns of Gene Expression* Regulation of Direct Cell-Type Specification in Early Development* The Secret of the Bilaterians: Abstract Regulatory Design in Building Adult Body Parts* Changes That Make New Forms: Gene Regulatory Systems and the Evolution of Body Plans

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.

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

An inspirational true story of devotion, courage and determination in the face of great tragedy - a story that will touch your heart.

Knowledge about the mechanisms of lung development has been growing rapidly, especially with regard to cellular and molecular aspects of growth and differentiation. This authoritative international volume reviews key aspects of lung development in health and disease by providing a comprehensive review of the complex series of cellular and molecular interactions required for lung development. It covers such topics as pulmonary hypoplasia, effects of malnutrition, and pulmaonary angiogenesis. An indispensable reference for all those involved in studying or treating lung disease in neonates and children, the book offers a unique view of the development of this essential organ.