Author
Kathryn V. Anderson
Other affiliations: Kettering University, Cornell University
Bio: Kathryn V. Anderson is an academic researcher from Memorial Sloan Kettering Cancer Center. The author has contributed to research in topics: Cilium & Gastrulation. The author has an hindex of 64, co-authored 122 publications receiving 20049 citations. Previous affiliations of Kathryn V. Anderson include Kettering University & Cornell University.
Papers published on a yearly basis
Papers
More filters
TL;DR: A role for Dicer, and, by implication, the RNAi machinery, in maintaining the stem cell population during early mouse development is suggested.
Abstract: To address the biological function of RNA interference (RNAi)-related pathways in mammals, we disrupted the gene Dicer1 in mice. Loss of Dicer1 lead to lethality early in development, with Dicer1-null embryos depleted of stem cells. Coupled with our inability to generate viable Dicer1-null embryonic stem (ES) cells, this suggests a role for Dicer, and, by implication, the RNAi machinery, in maintaining the stem cell population during early mouse development.
1,966 citations
TL;DR: The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction, and the cilium represents a nexus for signalling pathways during development.
Abstract: The primary cilium has recently stepped into the spotlight, as a flood of data show that this organelle has crucial roles in vertebrate development and human genetic diseases. Cilia are required for the response to developmental signals, and evidence is accumulating that the primary cilium is specialized for hedgehog signal transduction. The formation of cilia, in turn, is regulated by other signalling pathways, possibly including the planar cell polarity pathway. The cilium therefore represents a nexus for signalling pathways during development. The connections between cilia and developmental signalling have begun to clarify the basis of human diseases associated with ciliary dysfunction.
1,669 citations
TL;DR: Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 (the Hedgehog receptor) and upstream of direct targets of hedgehog signalling.
Abstract: Intraflagellar transport (IFT) proteins were first identified as essential factors for the growth and maintenance of flagella in the single-celled alga Chlamydomonas reinhardtii. In a screen for embryonic patterning mutations induced by ethylnitrosourea, here we identify two mouse mutants, wimple (wim) and flexo (fxo), that lack ventral neural cell types and show other phenotypes characteristic of defects in Sonic hedgehog signalling. Both mutations disrupt IFT proteins: the wim mutation is an allele of the previously uncharacterized mouse homologue of IFT172; and fxo is a new hypomorphic allele of polaris, the mouse homologue of IFT88. Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 (the Hedgehog receptor) and upstream of direct targets of Hedgehog signalling. Our data show that IFT machinery has an essential and vertebrate-specific role in Hedgehog signal transduction.
1,345 citations
TL;DR: The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor-NF-kappa B pathway in mammals are homologous signal transduction pathways that mediate several different biological responses.
Abstract: The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor (IL-1R)-NF-kappa B pathway in mammals are homologous signal transduction pathways that mediate several different biological responses. In Drosophila, genetic analysis of dorsal-ventral patterning of the embryo has defined the series of genes that mediate the Toll-Dorsal pathway. Binding of extracellular ligand activates the transmembrane receptor Toll, which requires the novel protein Tube to activate the cytoplasmic serine/threonine kinase Pelle. Pelle activity controls the degradation of the Cactus protein, which is present in a cytoplasmic complex with the Dorsal protein. Once Cactus is degraded in response to signal, Dorsal is free to move into the nucleus where it regulates transcription of specific target genes. The Toll, tube, pelle, cactus, and dorsal genes also appear to be involved in Drosophila immune response. Because the IL-1R-NF-kappa B pathway plays a role in vertebrate innate immunity and because plant homologues of the Toll-Dorsal pathway are important in plant disease resistance, it is likely that this pathway arose before the divergence of plants and animals as a defense against pathogens.
846 citations
TL;DR: It is shown here that mouse embryos that lack both Ift172 and Smo are identical to IFT172 single mutants, which indicates that Ift 172 acts downstream of Smo, which means that IFT mutants have a weaker neural patterning phenotype than Smo mutants.
Abstract: The intraflagellar transport (IFT) proteins Ift172/Wimple and Polaris/Ift88 and the anterograde IFT motor kinesin-II are required for the production and maintenance of cilia. These proteins are also required for the activation of targets of the mouse Hedgehog (Hh) pathway by Gli transcription factors. The phenotypes of the IFT mutants, however, are not identical to mutants that lack Smoothened (Smo), an essential activator of the Hh pathway. We show here that mouse embryos that lack both Ift172 and Smo are identical to Ift172 single mutants, which indicates that Ift172 acts downstream of Smo. Ift172 mutants have a weaker neural patterning phenotype than Smo mutants, because Ift172, but not Smo, is required for proteolytic processing of Gli3 to its repressor form. Dnchc2 and Kif3a, essential subunits of the retrograde and anterograde IFT motors, are also required for both formation of Gli activator and proteolytic processing of Gli3. As a result, IFT mutants display a loss of Hh signaling phenotype in the neural tube, where Gli activators play the major role in pattern formation, and a gain of Hh signaling phenotype in the limb, where Gli3 repressor plays the major role. Because both anterograde and retrograde IFT are essential for positive and negative responses to Hh, and because cilia are present on Hh responsive cells, it is likely that cilia act as organelles that are required for all activity of the mouse Hh pathway.
799 citations
Cited by
More filters
TL;DR: It is found that intraflagellar transport 20 mediates the ability of Ror2 signaling to induce the invasiveness of tumors that lack primary cilia, and IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex.
Abstract: Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
13,354 citations
TL;DR: This is the first complete genome sequence of a plant and provides the foundations for more comprehensive comparison of conserved processes in all eukaryotes, identifying a wide range of plant-specific gene functions and establishing rapid systematic ways to identify genes for crop improvement.
Abstract: The flowering plant Arabidopsis thaliana is an important model system for identifying genes and determining their functions. Here we report the analysis of the genomic sequence of Arabidopsis. The sequenced regions cover 115.4 megabases of the 125-megabase genome and extend into centromeric regions. The evolution of Arabidopsis involved a whole-genome duplication, followed by subsequent gene loss and extensive local gene duplications, giving rise to a dynamic genome enriched by lateral gene transfer from a cyanobacterial-like ancestor of the plastid. The genome contains 25,498 genes encoding proteins from 11,000 families, similar to the functional diversity of Drosophila and Caenorhabditis elegans--the other sequenced multicellular eukaryotes. Arabidopsis has many families of new proteins but also lacks several common protein families, indicating that the sets of common proteins have undergone differential expansion and contraction in the three multicellular eukaryotes. This is the first complete genome sequence of a plant and provides the foundations for more comprehensive comparison of conserved processes in all eukaryotes, identifying a wide range of plant-specific gene functions and establishing rapid systematic ways to identify genes for crop improvement.
8,742 citations
TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
8,642 citations
TL;DR: Microbial recognition by Toll-like receptors helps to direct adaptive immune responses to antigens derived from microbial pathogens to distinguish infectious nonself from noninfectious self.
Abstract: ▪ Abstract The innate immune system is a universal and ancient form of host defense against infection. Innate immune recognition relies on a limited number of germline-encoded receptors. These receptors evolved to recognize conserved products of microbial metabolism produced by microbial pathogens, but not by the host. Recognition of these molecular structures allows the immune system to distinguish infectious nonself from noninfectious self. Toll-like receptors play a major role in pathogen recognition and initiation of inflammatory and immune responses. Stimulation of Toll-like receptors by microbial products leads to the activation of signaling pathways that result in the induction of antimicrobial genes and inflammatory cytokines. In addition, stimulation of Toll-like receptors triggers dendritic cell maturation and results in the induction of costimulatory molecules and increased antigen-presenting capacity. Thus, microbial recognition by Toll-like receptors helps to direct adaptive immune responses ...
8,041 citations
TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
Abstract: MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. The two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events. Since then, hundreds of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. MicroRNAs have diverse expression patterns and might regulate various developmental and physiological processes. Their discovery adds a new dimension to our understanding of complex gene regulatory networks.
6,282 citations