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Radford, SJ, Nguyen AL, Schindler K, McKim KS.  2016.  The chromosomal basis of meiotic acentrosomal spindle assembly and function in oocytes.. Chromosoma. Abstract
Several aspects of meiosis are impacted by the absence of centrosomes in oocytes. Here, we review four aspects of meiosis I that are significantly affected by the absence of centrosomes in oocyte spindles. One, microtubules tend to assemble around the chromosomes. Two, the organization of these microtubules into a bipolar spindle is directed by the chromosomes. Three, chromosome bi-orientation and attachment to microtubules from the correct pole require modification of the mechanisms used in mitotic cells. Four, chromosome movement to the poles at anaphase cannot rely on polar anchoring of spindle microtubules by centrosomes. Overall, the chromosomes are more active participants during acentrosomal spindle assembly in oocytes, compared to mitotic and male meiotic divisions where centrosomes are present. The chromosomes are endowed with information that can direct the meiotic divisions and dictate their own behavior in oocytes. Processes beyond those known from mitosis appear to be required for their bi-orientation at meiosis I. As mitosis occurs without centrosomes in many systems other than oocytes, including all plants, the concepts discussed here may not be limited to oocytes. The study of meiosis in oocytes has revealed mechanisms that are operating in mitosis and will probably continue to do so.
Radford, SJ, Jang JK, McKim KS.  2012.  The Chromosomal Passenger Complex is required for Meiotic Acentrosomal Spindle Assembly and Chromosome Bi-orientation. Genetics. 192:417-429. AbstractWebsite
During meiosis in the females of many species, spindle assembly occurs in the absence of the microtubule-organizing centers called centrosomes. In the absence of centrosomes, the nature of the chromosome-based signal that recruits microtubules to promote spindle assembly as well as how spindle bipolarity is established and the chromosomes orient correctly towards the poles is not known. To address these questions, we focused on the chromosomal passenger complex (CPC). We have found that the CPC localizes in a ring around the meiotic chromosomes that is aligned with the axis of the spindle at all stages. Using new methods which dramatically increase the effectiveness of RNAi in the germline, we show that the CPC interacts with Drosophila oocyte chromosomes and is required for the assembly of spindle microtubules. Furthermore, chromosome bi-orientation and the localization of the central spindle kinesin-6 protein Subito, which is required for spindle bipolarity, depend on the CPC components Aurora B and Incenp. Based on these data we propose that the ring of CPC around the chromosomes regulates multiple aspects of meiotic cell division including spindle assembly, the establishment of bipolarity, the recruitment of important spindle organization factors, and the bi-orientation of homologous chromosomes.
Radford, SJ, McKim KS.  2016.  Techniques for Imaging Prometaphase and Metaphase of Meiosis I in Fixed Drosophila Oocytes.. Journal of visualized experiments : JoVE. (116) Abstract
Chromosome segregation in human oocytes is error prone, resulting in aneuploidy, which is the leading genetic cause of miscarriage and birth defects. The study of chromosome behavior in oocytes from model organisms holds much promise to uncover the molecular basis of the susceptibility of human oocytes to aneuploidy. Drosophila melanogaster is amenable to genetic manipulation, with over 100 years of research, community, and technique development. Visualizing chromosome behavior and spindle assembly in Drosophila oocytes has particular challenges, however, due primarily to the presence of membranes surrounding the oocyte that are impenetrable to antibodies. We describe here protocols for the collection, preparation, and imaging of meiosis I spindle assembly and chromosome behavior in Drosophila oocytes, which allow the molecular dissection of chromosome segregation in this important model organism.
Radford, SJ, Harrison AM, McKim KS.  2012.  Microtubule-depolymerizing Kinesin KLP10A Restricts the Length of the Acentrosomal Meiotic Spindle in Drosophila Females. Genetics. 192:431-440. AbstractWebsite
During cell division, a bipolar array of microtubules forms the spindle through which the forces required for chromosome segregation are transmitted. Interestingly, the spindle as a whole is stable enough to support these forces even though it is composed of dynamic microtubules, which are constantly undergoing periods of growth and shrinkage. Indeed, the regulation of microtubule dynamics is essential to the integrity and function of the spindle. We show here that a member of an important class of microtubule-depolymerizing kinesins, KLP10A, is required for the proper organization of the acentrosomal meiotic spindle in Drosophila melanogaster oocytes. In the absence of KLP10A, microtubule length is not controlled, resulting in extraordinarily long and disorganized spindles. In addition, the interactions between chromosomes and spindle microtubules are disturbed and can result in the loss of contact. These results indicate that the regulation of microtubule dynamics through KLP10A plays a critical role in restricting the length and maintaining bipolarity of the acentrosomal meiotic spindle and in promoting the contacts that the chromosomes make with microtubules required for meiosis I segregation.
Radford, SJ, Go A MM, McKim KS.  2016.  Cooperation Between Kinesin Motors Promotes Spindle Symmetry and Chromosome Organization in Oocytes.. Genetics. Abstract
The oocyte spindle in most animal species is assembled in the absence of the microtubule-organizing centers called centrosomes. Without the organization provided by centrosomes, acentrosomal meiotic spindle organization may rely heavily on the bundling of microtubules by kinesin motor proteins. Indeed, the minus-end directed kinesin-14 NCD and the plus-end directed kinesin-6 Subito are known to be required for oocyte spindle organization in Drosophila melanogaster How multiple microtubule-bundling kinesins interact to produce a functional acentrosomal spindle is not known. In addition, there have been few studies on the meiotic function of one of the most important microtubule-bundlers in mitotic cells, the kinesin-5 KLP61F. We have found that the kinesin-5 KLP61F is required for spindle and centromere symmetry in oocytes. The asymmetry observed in the absence of KLP61F depends on NCD, the kinesin-12 KLP54D, and the microcephaly protein ASP. In contrast, KLP61F and Subito work together in maintaining a bipolar spindle. We propose that the prominent central spindle, stabilized by Subito, provides the framework for the coordination of multiple microtubule-bundling activities. The activities of several proteins, including NCD, KLP54D, and ASP, generate asymmetries within the acentrosomal spindle, while KLP61F and Subito balance these forces resulting in the capacity to accurately segregate chromosomes.
Radford, SJ, Hoang TL, Gluszek AA, Ohkura H, McKim KS.  2015.  Lateral and End-On Kinetochore Attachments Are Coordinated to Achieve Bi-orientation in Drosophila Oocytes. PLoS Genetics. 11(10):e1005605.Website
Ramsey, KM, Osborne ML, Vvedenskaya IO, Su C, Nickels BE, Dove SL.  2015.  Ubiquitous promoter-localization of essential virulence regulators in Francisella tularensis.. PLoS Pathog. 11(4):e1004793.
Rauskolb, C, Irvine KD.  1999.  Notch-mediated segmentation and growth control of the Drosophila leg. Developmental Biology. 210:339-50. AbstractWebsite
The possession of segmented appendages is a defining characteristic of the arthropods. By analyzing both loss-of-function and ectopic expression experiments, we show that the Notch signaling pathway plays a fundamental role in the segmentation and growth of the Drosophila leg. Local activation of Notch is necessary and sufficient to promote the formation of joints between segments. This segmentation process requires the participation of the Notch ligands, Serrate and Delta, as well as Fringe. These three proteins are each expressed in the developing leg and antennal imaginal discs in a segmentally repeated pattern that is regulated downstream of the action of Wingless and Decapentaplegic. Our studies further show that Notch activation is both necessary and sufficient to promote leg growth. We also identify target genes regulated both positively and negatively downstream of Notch signaling that are required for normal leg development. Together, these observations outline a regulatory hierarchy for the segmentation and growth of the leg. The Notch pathway is also deployed for segmentation during vertebrate somitogenesis, which raises the possibility of a common origin for the segmentation of these distinct tissues.
Rauskolb, C, Sun S, Sun G, Pan Y, Irvine KD.  2014.  Cytoskeletal Tension Inhibits Hippo Signaling through an Ajuba-Warts Complex.. Cell. 158:143-156. AbstractWebsite
Mechanical forces have been proposed to modulate organ growth, but a molecular mechanism that links them to growth regulation in vivo has been lacking. We report that increasing tension within the cytoskeleton increases Drosophila wing growth, whereas decreasing cytoskeletal tension decreases wing growth. These changes in growth can be accounted for by changes in the activity of Yorkie, a transcription factor regulated by the Hippo pathway. The influence of myosin activity on Yorkie depends genetically on the Ajuba LIM protein Jub, a negative regulator of Warts within the Hippo pathway. We further show that Jub associates with α-catenin and that its localization to adherens junctions and association with α-catenin are promoted by cytoskeletal tension. Jub recruits Warts to junctions in a tension-dependent manner. Our observations delineate a mechanism that links cytoskeletal tension to regulation of Hippo pathway activity, providing a molecular understanding of how mechanical forces can modulate organ growth.
Rauskolb, C, Pan G, Reddy BVVG, Oh H, Irvine KD.  2011.  Zyxin links fat signaling to the hippo pathway. PLoS Biology. 9:e1000624. AbstractWebsite
The Hippo signaling pathway has a conserved role in growth control and is of fundamental importance during both normal development and oncogenesis. Despite rapid progress in recent years, key steps in the pathway remain poorly understood, in part due to the incomplete identification of components. Through a genetic screen, we identified the Drosophila Zyxin family gene, Zyx102 (Zyx), as a component of the Hippo pathway. Zyx positively regulates the Hippo pathway transcriptional co-activator Yorkie, as its loss reduces Yorkie activity and organ growth. Through epistasis tests, we position the requirement for Zyx within the Fat branch of Hippo signaling, downstream of Fat and Dco, and upstream of the Yorkie kinase Warts, and we find that Zyx is required for the influence of Fat on Warts protein levels. Zyx localizes to the sub-apical membrane, with distinctive peaks of accumulation at intercellular vertices. This partially overlaps the membrane localization of the myosin Dachs, which has similar effects on Fat-Hippo signaling. Co-immunoprecipitation experiments show that Zyx can bind to Dachs and that Dachs stimulates binding of Zyx to Warts. We also extend characterization of the Ajuba LIM protein Jub and determine that although Jub and Zyx share C-terminal LIM domains, they regulate Hippo signaling in distinct ways. Our results identify a role for Zyx in the Hippo pathway and suggest a mechanism for the role of Dachs: because Fat regulates the localization of Dachs to the membrane, where it can overlap with Zyx, we propose that the regulated localization of Dachs influences downstream signaling by modulating Zyx-Warts binding. Mammalian Zyxin proteins have been implicated in linking effects of mechanical strain to cell behavior. Our identification of Zyx as a regulator of Hippo signaling thus also raises the possibility that mechanical strain could be linked to the regulation of gene expression and growth through Hippo signaling.
Rauskolb, C, Correia T, Irvine KD.  1999.  Fringe-dependent separation of dorsal and ventral cells in the Drosophila wing. Nature. 401:476-80. AbstractWebsite
The separation of cells into populations that do not intermix, termed compartments, is a fundamental organizing principle during development. Dorsal-ventral compartmentalization of the Drosophila wing is regulated downstream of the apterous (ap) gene, which encodes a transcription factor that specifies dorsal wing fate. fringe (fng) is normally expressed by dorsal cells downstream of ap; here we show that fng plays a key role in dorsal-ventral compartmentalization. Loss of fng function causes dorsal cells to violate the compartment boundary, and ectopic expression of the Fng protein causes ventral cells to violate thecompartment boundary. Fng modulates signalling through the Notch receptor. Notch and its ligands are essential for formation of the dorsal-ventral compartment border, and repositioning the stripe of Notch activation that is normally established there appears to reposition the compartment border. However, activation of Notch does not itself confer either dorsal or ventral cell location, and fng can influence compartmentalization even within regions of ubiquitous Notch activation. Our results indicate that the primary mechanism by which fng establishes a compartment border is by positioning a stripe of Notch activation, but also that fng may exert additional influences on compartmentalization.
Reddy, BVVG, Irvine KD.  2013.  Regulation of Hippo Signaling by EGFR-MAPK Signaling through Ajuba Family Proteins.. Developmental Cell. 24:459-471. AbstractWebsite
EGFR and Hippo signaling pathways both control growth and, when dysregulated, contribute to tumorigenesis. We find that EGFR activates the Hippo pathway transcription factor Yorkie and demonstrate that Yorkie is required for the influence of EGFR on cell proliferation in Drosophila. EGFR regulates Yorkie through the influence of its Ras-MAPK branch on the Ajuba LIM protein Jub. Jub is epistatic to EGFR and Ras for Yorkie regulation, Jub is subject to MAPK-dependent phosphorylation, and EGFR-Ras-MAPK signaling enhances Jub binding to the Yorkie kinase Warts and the adaptor protein Salvador. An EGFR-Hippo pathway link is conserved in mammals, as activation of EGFR or RAS activates the Yorkie homolog YAP, and EGFR-RAS-MAPK signaling promotes phosphorylation of the Ajuba family protein WTIP and also enhances WTIP binding to the Warts and Salvador homologs LATS and WW45. Our observations implicate the Hippo pathway in EGFR-mediated tumorigenesis and identify a molecular link between these pathways.
Reddy, BVVG, Irvine KD.  2008.  The Fat and Warts signaling pathways: new insights into their regulation, mechanism and conservation. Development (Cambridge, England). 135:2827-38. AbstractWebsite
A cassette of cytoplasmic Drosophila tumor suppressors, including the kinases Hippo and Warts, has recently been linked to the transmembrane tumor suppressor Fat. These proteins act within interconnected signaling pathways, the principal functions of which are to control the growth and polarity of developing tissues. Recent studies have enhanced our understanding of the basis for signal transduction by Fat and Warts pathways, including the identification of a DNA-binding protein at the end of the pathway, have established the conservation of Fat and Warts signaling from flies to mammals, and have given us new insights into their regulation and biological functions.
Reddy, BVVG, Rauskolb C, Irvine KD.  2010.  Influence of fat-hippo and notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia. Development (Cambridge, England). 137:2397-408. AbstractWebsite
The Drosophila optic lobe develops from neuroepithelial cells, which function as symmetrically dividing neural progenitors. We describe here a role for the Fat-Hippo pathway in controlling the growth and differentiation of Drosophila optic neuroepithelia. Mutation of tumor suppressor genes within the pathway, or expression of activated Yorkie, promotes overgrowth of neuroepithelial cells and delays or blocks their differentiation; mutation of yorkie inhibits growth and accelerates differentiation. Neuroblasts and other neural cells, by contrast, appear unaffected by Yorkie activation. Neuroepithelial cells undergo a cell cycle arrest before converting to neuroblasts; this cell cycle arrest is regulated by Fat-Hippo signaling. Combinations of cell cycle regulators, including E2f1 and CyclinD, delay neuroepithelial differentiation, and Fat-Hippo signaling delays differentiation in part through E2f1. We also characterize roles for Jak-Stat and Notch signaling. Our studies establish that the progression of neuroepithelial cells to neuroblasts is regulated by Notch signaling, and suggest a model in which Fat-Hippo and Jak-Stat signaling influence differentiation by their acceleration of cell cycle progression and consequent impairment of Delta accumulation, thereby modulating Notch signaling. This characterization of Fat-Hippo signaling in neuroepithelial growth and differentiation also provides insights into the potential roles of Yes-associated protein in vertebrate neural development and medullablastoma.
Reinberg, D, Orphanides G, Ebright R, Akoulitchev S, Carcamo J, Cho H, Cortes P, Drapkin R, Flores O, Ha I et al..  1998.  The RNA polymerase II general transcription factors: past, present, and future.. Cold Spring Harbor symposia on quantitative biology. 63:83-103.
Renfrow, MB, Naryshkin N, Lewis ML, Chen H-T, Ebright RH, Scott RA.  2004.  Transcription factor B contacts promoter DNA near the transcription start site of the archaeal transcription initiation complex.. The Journal of biological chemistry. 279(4):2825-31. Abstract
Transcription initiation in all three domains of life requires the assembly of large multiprotein complexes at DNA promoters before RNA polymerase (RNAP)-catalyzed transcript synthesis. Core RNAP subunits show homology among the three domains of life, and recent structural information supports this homology. General transcription factors are required for productive transcription initiation complex formation. The archaeal general transcription factors TATA-element-binding protein (TBP), which mediates promoter recognition, and transcription factor B (TFB), which mediates recruitment of RNAP, show extensive homology to eukaryal TBP and TFIIB. Crystallographic information is becoming available for fragments of transcription initiation complexes (e.g. RNAP, TBP-TFB-DNA, TBP-TFIIB-DNA), but understanding the molecular topography of complete initiation complexes still requires biochemical and biophysical characterization of protein-protein and protein-DNA interactions. In published work, systematic site-specific protein-DNA photocrosslinking has been used to define positions of RNAP subunits and general transcription factors in bacterial and eukaryal initiation complexes. In this work, we have used systematic site-specific protein-DNA photocrosslinking to define positions of RNAP subunits and general transcription factors in an archaeal initiation complex. Employing a set of 41 derivatized DNA fragments, each having a phenyl azide photoactivable crosslinking agent incorporated at a single, defined site within positions -40 to +1 of the gdh promoter of the hyperthermophilic marine archaea, Pyrococcus furiosus (Pf), we have determined the locations of PfRNAP subunits PfTBP and PfTFB relative to promoter DNA. The resulting topographical information supports the striking homology with the eukaryal initiation complex and permits one major new conclusion, which is that PfTFB interacts with promoter DNA not only in the TATA-element region but also in the transcription-bubble region, near the transcription start site. Comparison with crystallographic information implicates the PfTFB N-terminal domain in the interaction with the transcription-bubble region. The results are discussed in relation to the known effects of substitutions in the TFB and TFIIB N-terminal domains on transcription initiation and transcription start-site selection.
Revyakin, A, Ebright RH, Strick TR.  2004.  Promoter unwinding and promoter clearance by RNA polymerase: detection by single-molecule DNA nanomanipulation.. Proceedings of the National Academy of Sciences of the United States of America. 101(14):4776-80. Abstract
By monitoring the end-to-end extension of a mechanically stretched, supercoiled, single DNA molecule, we have been able directly to observe the change in extension associated with unwinding of approximately one turn of promoter DNA by RNA polymerase (RNAP). By performing parallel experiments with negatively and positively supercoiled DNA, we have been able to deconvolute the change in extension caused by RNAP-dependent DNA unwinding (with approximately 1-bp resolution) and the change in extension caused by RNAP-dependent DNA compaction (with approximately 5-nm resolution). We have used this approach to quantify the extent of unwinding and compaction, the kinetics of unwinding and compaction, and effects of supercoiling, sequence, ppGpp, and nucleotides. We also have used this approach to detect promoter clearance and promoter recycling by successive RNAP molecules. We find that the rate of formation and the stability of the unwound complex depend profoundly on supercoiling and that supercoiling exerts its effects mechanically (through torque), and not structurally (through the number and position of supercoils). The approach should permit analysis of other nucleic-acid-processing factors that cause changes in DNA twist and/or DNA compaction.
Revyakin, A, Ebright RH, Strick TR.  2005.  Single-molecule DNA nanomanipulation: improved resolution through use of shorter DNA fragments.. Nature methods. 2(2):127-38.
Revyakin, A, Liu C, Ebright RH, Strick TR.  2006.  Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching.. Science (New York, N.Y.). 314(5802):1139-43. Abstract
Using single-molecule DNA nanomanipulation, we show that abortive initiation involves DNA "scrunching"--in which RNA polymerase (RNAP) remains stationary and unwinds and pulls downstream DNA into itself--and that scrunching requires RNA synthesis and depends on RNA length. We show further that promoter escape involves scrunching, and that scrunching occurs in most or all instances of promoter escape. Our results support the existence of an obligatory stressed intermediate, with approximately one turn of additional DNA unwinding, in escape and are consistent with the proposal that stress in this intermediate provides the driving force to break RNAP-promoter and RNAP-initiation-factor interactions in escape.
Revyakin, A, Allemand JF, Croquette V, Ebright RH, Strick TR.  2003.  Single-molecule DNA nanomanipulation: detection of promoter-unwinding events by RNA polymerase.. Methods in enzymology. 370:577-98.
Robb, NC, Cordes T, Hwang L C, Gryte K, Duchi D, Craggs TD, Santoso Y, Weiss S, Ebright RH, Kapanidis AN.  2013.  The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection.. Journal of molecular biology. 425:875-885. Abstract
Bacterial transcription is initiated after RNA polymerase (RNAP) binds to promoter DNA, melts ~14 base-pairs around the transcription start site, and forms a single-stranded "transcription bubble" within a catalytically active RNAP-DNA open complex (RP(o)). There is significant flexibility in the transcription start site, which causes variable spacing between the promoter elements and the start site; this in turn causes differences in the length and sequence at the 5' end of RNA transcripts, and can be important for gene regulation. The start-site variability also implies the presence of some flexibility in the positioning of the DNA relative to the RNAP active site in RP(o). The flexibility may occur in the positioning of the transcription bubble prior to RNA synthesis and may reflect bubble expansion ("scrunching") or bubble contraction ("unscrunching"). Here, we assess the presence of dynamic flexibility in RP(o) with single-molecule Förster Resonance Energy Transfer. We obtain experimental evidence for dynamic flexibility in RP(o) using different FRET rulers and labelling positions. An analysis of FRET distributions of RP(o) using burst variance analysis reveals conformational fluctuations in RP(o) in the millisecond timescale. Further experiments using subsets of nucleotides and DNA mutations allowed us to reprogram the transcription start sites, in a way that can be described by repositioning of the single-stranded transcription bubble relative to the RNAP active site within RP(o). Our study marks the first experimental observation of conformational dynamics in the transcription bubble of RP(o) and indicates that DNA dynamics within the bubble affect the search for transcription start sites.
Roberts, AF, Gumienny TL, Gleason RJ, Wang H, Padgett RW.  2010.  Regulation of genes affecting body size and innate immunity by the DBL-1/BMP-like pathway in Caenorhabditis elegans.. BMC Dev Biol.. 10:61.
Robins, H, Li Y, Padgett RW.  2005.  Incorporating structure to predict microRNA targets. Proceedings of the National Academy of Sciences of the United States of America. 102:4006-9. AbstractWebsite
MicroRNAs (miRNAs) are a recently discovered set of regulatory genes that constitute up to an estimated 1% of the total number of genes in animal genomes, including Caenorhabditis elegans, Drosophila, mouse, and humans [Lagos-Quintana, M., Rauhut, R., Lendeckel, W. & Tuschl, T. (2001) Science 294, 853-858; Lai, E. C., Tomancak, P., Williams, R. W. & Rubin, G.M. (2003) Genome Biol. 4, R42; Lau, N. C., Lim, L. P., Weinstein, E. G. & Bartel, D. P. (2001) Science 294, 858-862; Lee, R. C. & Ambros, V. (2001) Science 294, 862-8644; and Lee, R. C., Feinbaum, R. L. & Ambros, V. (1993) Cell 115, 787-798]. In animals, miRNAs regulate genes by attenuating protein translation through imperfect base pair binding to 3' UTR sequences of target genes. A major challenge in understanding the regulatory role of miRNAs is to accurately predict regulated targets. We have developed an algorithm for predicting targets that does not rely on evolutionary conservation. As one of the features of this algorithm, we incorporate the folded structure of mRNA. By using Drosophila miRNAs as a test case, we have validated our predictions in 10 of 15 genes tested. One of these validated genes is mad as a target for bantam. Furthermore, our computational and experimental data suggest that miRNAs have fewer targets than previously reported.
Robinson, DM, Go Y B, Greenblatt M, Dismukes CG.  2010.  Water Oxidation by λ-MnO2: Catalysis by the Cubical Mn4O4 Subcluster Obtained by Delithiation of Spinel LiMn2O4. Journal of the American Chemical Society. 132:11467-11469. AbstractWebsite
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Robinson, DM, Go Y B, Mui M, Gardner G, Zhang Z, Mastrogiovanni D, Garfunkel E, Li J, Greenblatt M, Dismukes CG.  2013.  Photochemical water oxidation by crystalline polymorphs of manganese oxides: structural requirements for catalysis.. Journal of the American Chemical Society. 135(9):3494-501. Abstract
Manganese oxides occur naturally as minerals in at least 30 different crystal structures, providing a rigorous test system to explore the significance of atomic positions on the catalytic efficiency of water oxidation. In this study, we chose to systematically compare eight synthetic oxide structures containing Mn(III) and Mn(IV) only, with particular emphasis on the five known structural polymorphs of MnO2. We have adapted literature synthesis methods to obtain pure polymorphs and validated their homogeneity and crystallinity by powder X-ray diffraction and both transmission and scanning electron microscopies. Measurement of water oxidation rate by oxygen evolution in aqueous solution was conducted with dispersed nanoparticulate manganese oxides and a standard ruthenium dye photo-oxidant system. No Ru was absorbed on the catalyst surface as observed by XPS and EDX. The post reaction atomic structure was completely preserved with no amorphization, as observed by HRTEM. Catalytic activities, normalized to surface area (BET), decrease in the series Mn2O3 > Mn3O4 ≫ λ-MnO2, where the latter is derived from spinel LiMn2O4 following partial Li(+) removal. No catalytic activity is observed from LiMn2O4 and four of the MnO2 polymorphs, in contrast to some literature reports with polydispersed manganese oxides and electro-deposited films. Catalytic activity within the eight examined Mn oxides was found exclusively for (distorted) cubic phases, Mn2O3 (bixbyite), Mn3O4 (hausmannite), and λ-MnO2 (spinel), all containing Mn(III) possessing longer Mn-O bonds between edge-sharing MnO6 octahedra. Electronically degenerate Mn(III) has antibonding electronic configuration e(g)(1) which imparts lattice distortions due to the Jahn-Teller effect that are hypothesized to contribute to structural flexibility important for catalytic turnover in water oxidation at the surface.