Artículo

Schröter, C.; Ares, S.; Morelli, L.G.; Isakova, A.; Hens, K.; Soroldoni, D.; Gajewski, M.; Jülicher, F.; Maerkl, S.J.; Deplancke, B.; Oates, A.C. "Topology and dynamics of the zebrafish segmentation clock core circuit" (2012) PLoS Biology. 10(7):11
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

During vertebrate embryogenesis, the rhythmic and sequential segmentation of the body axis is regulated by an oscillating genetic network termed the segmentation clock. We describe a new dynamic model for the core pace-making circuit of the zebrafish segmentation clock based on a systematic biochemical investigation of the network's topology and precise measurements of somitogenesis dynamics in novel genetic mutants. We show that the core pace-making circuit consists of two distinct negative feedback loops, one with Her1 homodimers and the other with Her7:Hes6 heterodimers, operating in parallel. To explain the observed single and double mutant phenotypes of her1, her7, and hes6 mutant embryos in our dynamic model, we postulate that the availability and effective stability of the dimers with DNA binding activity is controlled in a "dimer cloud" that contains all possible dimeric combinations between the three factors. This feature of our model predicts that Hes6 protein levels should oscillate despite constant hes6 mRNA production, which we confirm experimentally using novel Hes6 antibodies. The control of the circuit's dynamics by a population of dimers with and without DNA binding activity is a new principle for the segmentation clock and may be relevant to other biological clocks and transcriptional regulatory networks. © 2012 Schröter et al.

Registro:

Documento: Artículo
Título:Topology and dynamics of the zebrafish segmentation clock core circuit
Autor:Schröter, C.; Ares, S.; Morelli, L.G.; Isakova, A.; Hens, K.; Soroldoni, D.; Gajewski, M.; Jülicher, F.; Maerkl, S.J.; Deplancke, B.; Oates, A.C.
Filiación:Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Max Planck Institute for the Physics of Complex Systems, Dresden, Germany
CONICET, Departamento de Física, Universidad de Buenos Aires, Buenos Aires, Argentina
École Polytechnique Fédérale de Lausanne, Institute of Bioengineering, School of Life Sciences, Lausanne, Switzerland
Institute for Genetics, University of Cologne, Cologne, Germany
École Polytechnique Fédérale de Lausanne, Institute of Bioengineering, School of Engineering, Lausanne, Switzerland
University of Cambridge, Department of Genetics, Downing Street, Cambridge CB2 3EH, United Kingdom
Logic of Genomic Systems Laboratory, Centro Nacional de Biotecnologíla - CSIC, Calle Darwin 3, 28049 Madrid, Spain
Hamilton Bonaduz AG, Via Crusch 8, 7402 Bonaduz, Switzerland
Palabras clave:basic helix loop helix transcription factor; homodimer; messenger RNA; protein antibody; transcription factor Her1; transcription factor Her6; transcription factor Her6 antibody; transcription factor Her7; unclassified drug; basic helix loop helix transcription factor; her1 protein, zebrafish; HER7 protein, zebrafish; messenger RNA; repressor protein; transcription factor; zebrafish protein; animal experiment; animal tissue; article; controlled study; developmental biology; embryo; embryo development; embryo segmentation; embryonic structures; gene; her1 gene; her6 gene; her7 gene; messenger RNA synthesis; molecular clock; molecular dynamics; mutant; nonhuman; phenotype; prediction; protein DNA binding; protein function; protein stability; somitogenesis; transcription regulation; zebra fish; animal; biological model; biological rhythm; cytology; dimerization; enzyme specificity; feedback system; gene expression regulation; genetic transcription; genetics; metabolism; morphogenesis; prenatal development; promoter region; protein analysis; protein protein interaction; somite; two hybrid system; zebra fish; Danio rerio; Vertebrata; Animals; Basic Helix-Loop-Helix Transcription Factors; Biological Clocks; Body Patterning; Dimerization; Feedback, Physiological; Gene Expression Regulation, Developmental; Models, Biological; Phenotype; Promoter Regions, Genetic; Protein Interaction Mapping; Protein Interaction Maps; Protein Stability; Repressor Proteins; RNA, Messenger; Somites; Substrate Specificity; Transcription Factors; Transcription, Genetic; Two-Hybrid System Techniques; Zebrafish; Zebrafish Proteins
Año:2012
Volumen:10
Número:7
Página de inicio:11
DOI: http://dx.doi.org/10.1371/journal.pbio.1001364
Título revista:PLoS Biology
Título revista abreviado:PloS Biol.
ISSN:15449173
CODEN:PBLIB
CAS:Basic Helix-Loop-Helix Transcription Factors; HER7 protein, zebrafish; RNA, Messenger; Repressor Proteins; Transcription Factors; Zebrafish Proteins; her1 protein, zebrafish
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15449173_v10_n7_p11_Schroter

Referencias:

  • Dequeant, M.L., Pourquie, O., Segmental patterning of the vertebrate embryonic axis (2008) Nat Rev Genet, 9, pp. 370-382
  • Holley, S.A., The genetics and embryology of zebrafish metamerism (2007) Dev Dyn, 236, pp. 1422-1449
  • Oates, A.C., Morelli, L.G., Ares, S., Patterning embryos with oscillations: structure, function and dynamics of the vertebrate segmentation clock (2012) Development, 139, pp. 625-639
  • Dequeant, M.L., Glynn, E., Gaudenz, K., Wahl, M., Chen, J., A complex oscillating network of signaling genes underlies the mouse segmentation clock (2006) Science, 314, pp. 1595-1598
  • Krol, A.J., Roellig, D., Dequeant, M.L., Tassy, O., Glynn, E., Evolutionary plasticity of segmentation clock networks (2011) Development, 138, pp. 2783-2792
  • Palmeirim, I., Henrique, D., Ish-Horowicz, D., Pourquie, O., Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis (1997) Cell, 91, pp. 639-648
  • Masamizu, Y., Ohtsuka, T., Takashima, Y., Nagahara, H., Takenaka, Y., Real-time imaging of the somite segmentation clock: revelation of unstable oscillators in the individual presomitic mesoderm cells (2006) Proc Natl Acad Sci U S A, 103, pp. 1313-1318
  • Cinquin, O., Repressor dimerization in the zebrafish somitogenesis clock (2007) PLoS Comput Biol, 3, pp. e32. , doi:10.1371/journal.pcbi.0030032
  • Uriu, K., Morishita, Y., Iwasa, Y., Random cell movement promotes synchronization of the segmentation clock (2010) Proc Natl Acad Sci U S A, 107, pp. 4979-4984
  • Lewis, J., Autoinhibition with transcriptional delay: a simple mechanism for the zebrafish somitogenesis oscillator (2003) Curr Biol, 13, pp. 1398-1408
  • Oates, A.C., Ho, R.K., Hairy/E(spl)-related (Her) genes are central components of the segmentation oscillator and display redundancy with the Delta/Notch signaling pathway in the formation of anterior segmental boundaries in the zebrafish (2002) Development, 129, pp. 2929-2946
  • Henry, C.A., Urban, M.K., Dill, K.K., Merlie, J.P., Page, M.F., Two linked hairy/Enhancer of split-related zebrafish genes, her1 and her7, function together to refine alternating somite boundaries (2002) Development, 129, pp. 3693-3704
  • Giudicelli, F., Ozbudak, E.M., Wright, G.J., Lewis, J., Setting the tempo in development: an investigation of the zebrafish somite clock mechanism (2007) PLoS Biol, 5, pp. e150. , doi:10.1371/journal.pbio.0050150
  • Brend, T., Holley, S.A., Expression of the oscillating gene her1 is directly regulated by hairy/enhancer of split, T-box, and suppressor of hairless proteins in the zebrafish segmentation clock (2009) Dev Dyn, 238, pp. 2745-2759
  • Cooke, J., Zeeman, E.C., A clock and wavefront model for control of the number of repeated structures during animal morphogenesis (1976) J Theor Biol, 58, pp. 455-476
  • Gomez, C., Ozbudak, E.M., Wunderlich, J., Baumann, D., Lewis, J., Control of segment number in vertebrate embryos (2008) Nature, 454, pp. 335-339
  • Schroter, C., Oates, A.C., Segment number and axial identity in a segmentation clock period mutant (2010) Curr Biol, 20, pp. 1254-1258
  • Kawamura, A., Koshida, S., Hijikata, H., Sakaguchi, T., Kondoh, H., Zebrafish hairy/enhancer of split protein links FGF signaling to cyclic gene expression in the periodic segmentation of somites (2005) Genes Dev, 19, pp. 1156-1161
  • Maerkl, S.J., Quake, S.R., A systems approach to measuring the binding energy landscapes of transcription factors (2007) Science, 315, pp. 233-237
  • Gerber, D., Maerkl, S.J., Quake, S.R., An in vitro microfluidic approach to generating protein-interaction networks (2009) Nat Methods, 6, pp. 71-74
  • Maerkl, S.J., Quake, S.R., Experimental determination of the evolvability of a transcription factor (2009) Proc Natl Acad Sci U S A, 106, pp. 18650-18655
  • Spinner, D.S., Liu, S., Wang, S.W., Schmidt, J., Interaction of the myogenic determination factor myogenin with E12 and a DNA target: mechanism and kinetics (2002) J Mol Biol, 317, pp. 431-445
  • Fordyce, P.M., Gerber, D., Tran, D., Zheng, J., Li, H., De novo identification and biophysical characterization of transcription-factor binding sites with microfluidic affinity analysis (2010) Nat Biotechnol, 28, pp. 970-975
  • Walhout, A.J., Vidal, M., High-throughput yeast two-hybrid assays for large-scale protein interaction mapping (2001) Methods, 24, pp. 297-306
  • Deplancke, B., Dupuy, D., Vidal, M., Walhout, A.J., A gateway-compatible yeast one-hybrid system (2004) Genome Res, 14, pp. 2093-2101
  • Trofka, A., Schwendinger-Schreck, J., Brend, T., Pontius, W., Emonet, T., The Her7 node modulates the network topology of the zebrafish segmentation clock via sequestration of the Hes6 hub (2012) Development, 139, pp. 940-947
  • Holley, S.A., Julich, D., Rauch, G.J., Geisler, R., Nusslein-Volhard, C., her1 and the notch pathway function within the oscillator mechanism that regulates zebrafish somitogenesis (2002) Development, 129, pp. 1175-1183
  • Wienholds, E., van Eeden, F., Kosters, M., Mudde, J., Plasterk, R.H., Efficient target-selected mutagenesis in zebrafish (2003) Genome Res, 13, pp. 2700-2707
  • Julich, D., Hwee Lim, C., Round, J., Nicolaije, C., Schroeder, J., beamter/deltaC and the role of Notch ligands in the zebrafish somite segmentation, hindbrain neurogenesis and hypochord differentiation (2005) Dev Biol, 286, pp. 391-404
  • Gajewski, M., Sieger, D., Alt, B., Leve, C., Hans, S., Anterior and posterior waves of cyclic her1 gene expression are differentially regulated in the presomitic mesoderm of zebrafish (2003) Development, 130, pp. 4269-4278
  • Sieger, D., Ackermann, B., Winkler, C., Tautz, D., Gajewski, M., her1 and her13.2 are jointly required for somitic border specification along the entire axis of the fish embryo (2006) Dev Biol, 293, pp. 242-251
  • Herrgen, L., Schroter, C., Bajard, L., Oates, A.C., Multiple embryo time-lapse imaging of zebrafish development (2009) Methods Mol Biol, 546, pp. 243-254
  • Schroter, C., Herrgen, L., Cardona, A., Brouhard, G.J., Feldman, B., Dynamics of zebrafish somitogenesis (2008) Dev Dyn, 237, pp. 545-553
  • Rubinow, S.I., Segel, L.A., Positive and negative cooperativity (1991) Biological Kinetics, pp. 29-44. , In: Segel L. A, editors, Cambridge, Cambridge University Press
  • Zeiser, S., Liebscher, H.V., Tiedemann, H., Rubio-Aliaga, I., Przemeck, G.K., Number of active transcription factor binding sites is essential for the Hes7 oscillator (2006) Theor Biol Med Model, 3, p. 11
  • Singh, J., Padgett, R.A., Rates of in situ transcription and splicing in large human genes (2009) Nat Struct Mol Biol, 16, pp. 1128-1133
  • Sasai, Y., Kageyama, R., Tagawa, Y., Shigemoto, R., Nakanishi, S., Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split (1992) Genes Dev, 6, pp. 2620-2634
  • Ohsako, S., Hyer, J., Panganiban, G., Oliver, I., Caudy, M., Hairy function as a DNA-binding helix-loop-helix repressor of Drosophila sensory organ formation (1994) Genes Dev, 8, pp. 2743-2755
  • Hirata, H., Bessho, Y., Kokubu, H., Masamizu, Y., Yamada, S., Instability of Hes7 protein is crucial for the somite segmentation clock (2004) Nat Genet, 36, pp. 750-754
  • Monk, N.A., Oscillatory expression of Hes1, p53, and NF-kappaB driven by transcriptional time delays (2003) Curr Biol, 13, pp. 1409-1413
  • Lingbeck, J.M., Trausch-Azar, J.S., Ciechanover, A., Schwartz, A.L., E12 and E47 modulate cellular localization and proteasome-mediated degradation of MyoD and Id1 (2005) Oncogene, 24, pp. 6376-6384
  • Trausch-Azar, J.S., Lingbeck, J., Ciechanover, A., Schwartz, A.L., Ubiquitin-Proteasome-mediated degradation of Id1 is modulated by MyoD (2004) J Biol Chem, 279, pp. 32614-32619
  • Zhang, F., Lu, J., Liu, Z., Chen, A., Shen, J., Effects of nonlinear degradation of protein on the oscillatory dynamics in a simple gene regulatory network (2010) Physica A, 389, pp. 1286-1295
  • Buchler, N.E., Gerland, U., Hwa, T., Nonlinear protein degradation and the function of genetic circuits (2005) Proc Natl Acad Sci U S A, 102, pp. 9559-9564
  • Buchler, N.E., Louis, M., Molecular titration and ultrasensitivity in regulatory networks (2008) J Mol Biol, 384, pp. 1106-1119
  • Campanelli, M., Gedeon, T., Somitogenesis clock-wave initiation requires differential decay and multiple binding sites for clock protein (2010) PLoS Comput Biol, 6, pp. e1000728. , doi:10.1371/journal.pcbi.1000728
  • Bae, S., Bessho, Y., Hojo, M., Kageyama, R., The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation (2000) Development, 127, pp. 2933-2943
  • Massari, M.E., Murre, C., Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms (2000) Mol Cell Biol, 20, pp. 429-440
  • Fischer, A., Gessler, M., Delta-Notch-and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors (2007) Nucleic Acids Res, 35, pp. 4583-4596
  • Bessho, Y., Hirata, H., Masamizu, Y., Kageyama, R., Periodic repression by the bHLH factor Hes7 is an essential mechanism for the somite segmentation clock (2003) Genes Dev, 17, pp. 1451-1456
  • Bessho, Y., Sakata, R., Komatsu, S., Shiota, K., Yamada, S., Dynamic expression and essential functions of Hes7 in somite segmentation (2001) Genes Dev, 15, pp. 2642-2647
  • Ohtsuka, T., Ishibashi, M., Gradwohl, G., Nakanishi, S., Guillemot, F., Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation (1999) The EMBO Journal, 18, pp. 2196-2207
  • Leimeister, C., Dale, K., Fischer, A., Klamt, B., Hrabe de Angelis, M., Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors (2000) Dev Biol, 227, pp. 91-103
  • Bhattacharya, A., Baker, N.E., A network of broadly expressed HLH genes regulates tissue-specific cell fates (2011) Cell, 147, pp. 881-892
  • Oster, H., Yasui, A., van der Horst, G.T., Albrecht, U., Disruption of mCry2 restores circadian rhythmicity in mPer2 mutant mice (2002) Genes Dev, 16, pp. 2633-2638
  • Shankaran, S.S., Sieger, D., Schroter, C., Czepe, C., Pauly, M.C., Completing the set of h/E(spl) cyclic genes in zebrafish: her12 and her15 reveal novel modes of expression and contribute to the segmentation clock (2007) Dev Biol, 304, pp. 615-632
  • Sieger, D., Tautz, D., Gajewski, M., her11 is involved in the somitogenesis clock in zebrafish (2004) Dev Genes Evol, 214, pp. 393-406
  • Herrgen, L., Ares, S., Morelli, L.G., Schroter, C., Julicher, F., Intercellular coupling regulates the period of the segmentation clock (2010) Curr Biol
  • Morelli, L.G., Ares, S., Herrgen, L., Schroter, C., Julicher, F., Delayed coupling theory of vertebrate segmentation (2009) HFSP J, 3, pp. 55-66
  • Uriu, K., Morishita, Y., Iwasa, Y., Traveling wave formation in vertebrate segmentation (2009) J Theor Biol, 257, pp. 385-396
  • Hester, S.D., Belmonte, J.M., Gens, J.S., Clendenon, S.G., Glazier, J.A., A multi-cell, multi-scale model of vertebrate segmentation and somite formation (2011) PLoS Comput Biol, 7, pp. e1002155. , doi:10.1371/journal.pcbi.1002155
  • Santillan, M., Mackey, M.C., A proposed mechanism for the interaction of the segmentation clock and the determination front in somitogenesis (2008) PLoS One, 3, pp. e1561. , doi:10.1371/journal.pone.0001561
  • Rodriguez-Gonzalez, J.G., Santillan, M., Fowler, A.C., Mackey, M.C., The segmentation clock in mice: interaction between the Wnt and Notch signalling pathways (2007) Journal of Theoretical Biology, 248, pp. 37-47
  • Murray, P.J., Maini, P.K., Baker, R.E., The clock and wavefront model revisited (2011) Journal of Theoretical Biology, 283, pp. 227-238
  • Tiedemann, H.B., Schneltzer, E., Zeiser, S., Rubio-Aliaga, I., Wurst, W., Cell-based simulation of dynamic expression patterns in the presomitic mesoderm (2007) Journal of Theoretical Biology, 248, pp. 120-129
  • Novak, B., Tyson, J.J., Design principles of biochemical oscillators (2008) Nat Rev Mol Cell Biol, 9, pp. 981-991
  • Zeiser, S., Muller, J., Liebscher, V., Modeling the Hes1 oscillator (2007) J Comput Biol, 14, pp. 984-1000
  • Hens, K., Feuz, J., Isakova, A., Iagovitina, A., Massouras, A., Automated protein-DNA interaction screening of Drosophila regulatory elements (2011) Nat Methods in Press
  • Thorsen, T., Maerkl, S.J., Quake, S.R., Microfluidic large-scale integration (2002) Science, 298, pp. 580-584
  • Muller, M., Weizsacker, E., Campos-Ortega, J.A., Expression domains of a zebrafish homologue of the Drosophila pair-rule gene hairy correspond to primordia of alternating somites (1996) Development, 122, pp. 2071-2078
  • Deniziak, M., Thisse, C., Rederstorff, M., Hindelang, C., Thisse, B., Loss of selenoprotein N function causes disruption of muscle architecture in the zebrafish embryo (2007) Exp Cell Res, 313, pp. 156-167
  • Weinberg, E.S., Allende, M.L., Kelly, C.S., Abdelhamid, A., Murakami, T., Developmental regulation of zebrafish MyoD in wild-type, no tail and spadetail embryos (1996) Development, 122, pp. 271-280
  • Prince, V.E., Joly, L., Ekker, M., Ho, R.K., Zebrafish hox genes: genomic organization and modified colinear expression patterns in the trunk (1998) Development, 125, pp. 407-420
  • Riedel-Kruse, I.H., Muller, C., Oates, A.C., Synchrony dynamics during initiation, failure, and rescue of the segmentation clock (2007) Science, 317, pp. 1911-1915
  • Oates, A.C., Mueller, C., Ho, R.K., Cooperative function of deltaC and her7 in anterior segment formation (2005) Dev Biol, 280, pp. 133-149

Citas:

---------- APA ----------
Schröter, C., Ares, S., Morelli, L.G., Isakova, A., Hens, K., Soroldoni, D., Gajewski, M.,..., Oates, A.C. (2012) . Topology and dynamics of the zebrafish segmentation clock core circuit. PLoS Biology, 10(7), 11.
http://dx.doi.org/10.1371/journal.pbio.1001364
---------- CHICAGO ----------
Schröter, C., Ares, S., Morelli, L.G., Isakova, A., Hens, K., Soroldoni, D., et al. "Topology and dynamics of the zebrafish segmentation clock core circuit" . PLoS Biology 10, no. 7 (2012) : 11.
http://dx.doi.org/10.1371/journal.pbio.1001364
---------- MLA ----------
Schröter, C., Ares, S., Morelli, L.G., Isakova, A., Hens, K., Soroldoni, D., et al. "Topology and dynamics of the zebrafish segmentation clock core circuit" . PLoS Biology, vol. 10, no. 7, 2012, pp. 11.
http://dx.doi.org/10.1371/journal.pbio.1001364
---------- VANCOUVER ----------
Schröter, C., Ares, S., Morelli, L.G., Isakova, A., Hens, K., Soroldoni, D., et al. Topology and dynamics of the zebrafish segmentation clock core circuit. PloS Biol. 2012;10(7):11.
http://dx.doi.org/10.1371/journal.pbio.1001364