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Do we know anything about how left–right asymmetry is first established in the vertebrate embryo?

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References

  • Afzelius B.A. (1976). A human syndrome caused by immotile cilia. Science 193: 317–319

    Article  PubMed  CAS  Google Scholar 

  • Bartoloni L., Bloiun J.L., Pan Y., Gehrig C., Maiti A.K., Sacamuffa N., Rossier C., Jorissen M., Armengot M., Meeks M., et al. (2002). Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc. Natl. Acad. Sci. USA 99:10282–10286

    Article  PubMed  CAS  Google Scholar 

  • Bellomo D., Lander A., Harragan I., Brown N.A. (1996). Cell proliferation in mammalian gastrulation: The ventral node and notochord are relatively quiescent. Dev. Dyn. 205:471–485

    Article  PubMed  CAS  Google Scholar 

  • Brennan J., Norris D.P. and Robertson E.J. (2002). Nodal activity in the node governs left-right asymmetry. Genes and Dev. 16:2339–2344

    Article  PubMed  CAS  Google Scholar 

  • Brown N.A. and Wolpert L. (1990). The development of handedness in left/right asymmetry. Development 109:1–9

    PubMed  CAS  Google Scholar 

  • Brueckner M. (2001). Cilia propel the embryo in the right direction. Am. J. Med.Genet. 101:339–344

    Article  PubMed  CAS  Google Scholar 

  • Bunney T.D., De Boer A.H. and Levin M. (2003). Fusicoccin signaling reveals 14–3-3 protein function as a novel step in left–right patterning during amphibian embryogenesis. Development 130:4847–4858

    Article  PubMed  CAS  Google Scholar 

  • Cartwright J.H., Piro O., Taval I. (2004). Fluid dynamic basis of the embryonic development of left–right asymmetry in vertebrates. Proc. Natl. Acad. Sci. USA 101:7234–7239

    Article  PubMed  CAS  Google Scholar 

  • Collignon J., Varlet I., Robertson E.J. (1996). Relationship between asymmetric nodal expression and the direction of embryonic turning. Nature 381:155–158

    Article  PubMed  CAS  Google Scholar 

  • Essner J.J., Amack J.D., Nyholm M.K., Harris E.R. and Yost H.J. (2005). Kupffer’s vesicle is a ciliated organ of asymmetry in the zebrafish embryo that initiates left–right development of the brain, heart, and gut. Development 132:1247–1260

    Article  PubMed  CAS  Google Scholar 

  • Essner J.J., Vogan K.J., Wagner M.K. Tabin C.J., Yost H.J. and Brueckner M. (2002). Conserved function for embryonic nodal cilia. Nature 418:37–38

    Article  PubMed  CAS  Google Scholar 

  • Fischer A., Viebahn C., Blum M. (2002). Fgf8 acts as a right determinant during establishment of the left–right axis in the rabbit. Curr. Biol. 12:1807–1816

    Article  PubMed  CAS  Google Scholar 

  • Guichard C., Harricane M.C., Lafitte J.J., Godard P., Zaegel M., Tack V., Lalau G., Bouvagnet P. (2001). Axonemal dynein intermediate-chain gene (DNA11) mutations result in situs inversus and primary ciliary dyskinesia (Kartegener syndrome). Am. J. Hum. Genet. 68:1030–1035

    Article  PubMed  CAS  Google Scholar 

  • Huangfu D., Liu A., Rakeman A.S., Murcia N.S., Niswander L., Anderson K.V. (2003). Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426:83–87

    Article  PubMed  CAS  Google Scholar 

  • Igarashi P., Somlo S. (2002). Genetics and pathogenesis of polycystic kidney disease. J. Am. Soc. Nephrol. 13:2384–2398

    Article  PubMed  CAS  Google Scholar 

  • Kawakami Y., Raya, Á., Raya R.M., Rodríguez-Esteban C., Izpisúa Belmonte J.C. (2005). Retinoic acid signaling links left–right asymmetric patterning and bilaterally symmtric somitogenesis in the zebrafish embryo. Nature 435:165–171

    Article  PubMed  CAS  Google Scholar 

  • Kramer K.L., Barnette J.B. and Yost H.J. (2002). PKCgamma regulates syndecan-2 inside-out signaling during Xenopus left–right development. Cell 111:981–990

    Article  PubMed  CAS  Google Scholar 

  • Kramer K.L. and Yost H.J. (2002). Ectodermal syndecan-2 mediates left–right axis formation in migrating mesoderm as a cell-nonautomous Vg1 cofactor. Dev Cell 2:115–124

    Article  PubMed  CAS  Google Scholar 

  • Koulen P., Cai Y., Geng L., Maeda Y., Nishimura S., Witzgall, Ehrlich B.E. and Somlo S. (2002). Polycystin-2 is an intracellular calcium release channel. Nat. Cell Biol. 4:191–197

    Article  PubMed  CAS  Google Scholar 

  • Levin M. (2004). The embryonic origins of left–right asymmetry. Crit. Rev. Oral Biol. Med. 15:197–206

    Article  PubMed  Google Scholar 

  • Levin M., Johnson R.L., Stern C.D., Kuehn M., Tabin C. (1995). A molecular pathway determining left–right asymmetry in chick embryogenesis. Cell 82:803–814

    Article  PubMed  CAS  Google Scholar 

  • Levin M. and Mercola M. (1998). Gap junctions are involved in the early generation of left right asymmetry. Dev Biol. 203:90–105

    Article  PubMed  CAS  Google Scholar 

  • Levin M. and Mercola M. (1999). Gap junction-mediated transfer of left–right patterning signals in the early chick blastoderm is upstream of Shh asymmetry in the node. Development 126:4703–4714

    PubMed  CAS  Google Scholar 

  • Levin M. and Nascone N. (1997). Two molecular models of initial left–right asymmetry generation. Med. Hypoth. 49:429–435

    Article  CAS  Google Scholar 

  • Levin M., Pagan S., Roberts D.J., Cooke J., Kuehn M.R. and Tabin C.J. (1997). Left/right patterning signals and the independent regulation of different aspects of situs in the chick embryo. Dev Biol. 189:57–67

    Article  PubMed  CAS  Google Scholar 

  • Levin M., Thorlin T., Robinson K., Nogi T., Mercola M. (2002). Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left–right patterning. Cell 111:77–89

    Article  PubMed  CAS  Google Scholar 

  • Lowe L.A., Supp D.M., Sampath K., Yokoyama T., Wright C.V., Porter S.S., Overbeek P., Kuehn M.R. (1996). Conserved left–right asymmetry of nodal expression and alterations in murine situs inversus. Nature 381:158–161

    Article  PubMed  CAS  Google Scholar 

  • Marszalek J.R., Ruiz-Lozano P., Roberts E., Chien K.R. and Goldstein L.S. (1999). Situs inversus and embryonic ciliary morphogenesis defects in mouse mutants lacking the KIF3A subunit of kinesin-II. Proc. Natl. Acad. Sci. USA 96:5043–5048

    Article  PubMed  CAS  Google Scholar 

  • McGrath J., Somlo S., Mukawa S., Tian Y., Brueckner M. (2003). Two populations of node monocilia initiate left–right asymmetry in the mouse. Cell 114:61–73

    Article  PubMed  CAS  Google Scholar 

  • Meno C., Saijoh Y., Fujii H., Ikeda M., Yokoyama M., Toyoda Y., Hamada H. (1996). Left–right asymmetric gene expression of the TGFbeta-family member lefty in mouse embryos. Nature 381:151–155

    Article  PubMed  CAS  Google Scholar 

  • Meyers E.N. and Martin G.R. (1999). Differences in left–right axis pathways in mouse and chick: functions of FGF8 and SHH. Science 285:403–406

    Article  PubMed  CAS  Google Scholar 

  • Murcia N.S., Richards W.G., Yoder B.K., Mucenski M.L., Dunlap J.R. and Woychik R.P. (2000). The Oak Ridge Polycystic Kidney (orpk) disease gene is required for left–right axis determination. Development 127:2347–2355

    PubMed  CAS  Google Scholar 

  • Nauli S.M., Alenghat F.J., Luo Y., Williams E., Vassilev P., Li X., Elia A.E., Lu W., Brown E.M., Quinn S.J., Ingber D.E. and Zhou J. (2003). Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33:129–137

    Article  PubMed  CAS  Google Scholar 

  • Nonaka S., Tanaka Y., Okada Y., Takeda S., Harada A. Kanai Y., Kido, and Hirokawa N. (1998). Randomization of left–right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in miced lacking KIF3B motor protein. Cell 95:829–837

    Article  PubMed  CAS  Google Scholar 

  • Nonaka S., Shiratori H., Saijoh Y., Hamada H. (2002). Determination of left–right patterning of the mouse embryo by artificial nodal flow. Nature 418:96–99

    Article  PubMed  CAS  Google Scholar 

  • Nonaka S, Yoshiba S, Watanabe D, Ikeuchi S, Goto T, Marshall, W, Hamada H (2005) De novo formation of left–right asymmetry by posterior tilt of node cilia. PLoS Biol. in press

  • Olbrich H., Haffner K., Kisbert A., Volkel A., Voltz A., Sasmaz G., Reinhardt R., Hennig S., Lehrach H., Konitzko. N., et al. (2002). Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left–right asymmetry. Nat. Genet. 30:143–144

    Article  PubMed  CAS  Google Scholar 

  • Okada Y., Nonaka S., Saijoh Y., Hamada H., Hirokawa N. (1999). Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol. Cell 4:459–468

    Article  PubMed  CAS  Google Scholar 

  • Okada Y., Takeda S., Tanaka Y., Izpisua Belmonte, J-C, and Hirokawa N. (2005). Mechanism of nodal flow: a conserved symmetry breaking event in left–right axis determination. Cell 121:633–644

    Article  PubMed  CAS  Google Scholar 

  • Pennarum G., Escudier E., Chapelin C., Bridoux A.M., Cacheux V., Roger G., Clement A., Goossens M., Amselem S., Duriez B. (1999). Loss-of-function mutations in a human gene related to Chlamydomonas reinhardti dynein IC78 result in primary ciliary dyskinesia. Am. J. Hum. Genet. 65:1508–1519

    Article  PubMed  Google Scholar 

  • Pennekamp P., Karcher C., Fischer A., Schweickert A., Skryabin B., Horst J., Blum M., Dworniczak B. (2002). The ion channel polycystin-2 is required for left–right axis determination in mice. Curr. Biol. 12:938–943

    Article  PubMed  CAS  Google Scholar 

  • Praetorius H.A. and Spring K.R. (2001). Bending the MDCK primary channel cilium increases intracellular calcium. J. Membrane Biol. 184:71–79

    Article  CAS  Google Scholar 

  • Rankin C.T., Bunton C.T., Lawler A.M. and Lee S.-J. (2000). Regulation of left–right patterning in mice by growth/differentiation factor-1. Nat. Genet. 24:262–265

    Article  PubMed  CAS  Google Scholar 

  • Stern C., Yu R., Kakizuka A., Kintner C., Matthews L., Vale W. et al. (1995). Activin and its receptors during gastrulation and the later phases of mesoderm development in the chick embryo. Dev. Biol. 172: 192–205

    Article  PubMed  CAS  Google Scholar 

  • Sulik K., Dehart D.B., Inagaki T., Carson J.L., Vrablic T., Gesteland K., Schoenwolf G.C. (1994). Morphogenesis of the murine node and notochordal plate. Dev. Dyn. 201:260–278

    PubMed  CAS  Google Scholar 

  • Supp D.M., Witte D.P., Potter S.S. and Brueckner M. (1997). Mutation of an axonemal dynein affects left–right asymmetry in inversus viscerum mice. Nature 389:963–966

    Article  PubMed  CAS  Google Scholar 

  • Supp D.M., Brueckner M., Kuehn M.R., Witte D.P., Lowe L.A., McGrath J., Corrales J., Potter S.S. (1999). Targeted deletion of the ATP binding domain of left–right dynein confirms its role in specifying development of left–right asymmetries. Development 126:5495–5504

    PubMed  CAS  Google Scholar 

  • Tabin C.J. and Vogan K.J. (2003). A two-cilia model for vertebrate left–right axis specification. Genes and Dev. 17:1–6

    Article  PubMed  CAS  Google Scholar 

  • Takeda S., Yonekawa Y., Tanaka Y., Okada Y., Nonaka S., Hirokawa N. (1999). Left–right asymmetry and kinesin superfamily protein KIF3A: New insights in determination of laterality and mesoderm induction by kif3A−/+ mice analysis. J. Cell Biol: 145:825–836

    Article  PubMed  CAS  Google Scholar 

  • Tanaka Y., Okada Y. and Hirokawa N. (2005). FGF-induced leftward nodal flow of SHH/RA-containing vesicles is critical for laterality. Nature 435:172–177

    Article  PubMed  CAS  Google Scholar 

  • Zhang X.M., Ramalho-Santos M. and McMahon A.P. (2001). Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell 105:781–792

    Article  PubMed  CAS  Google Scholar 

  • Zhang Q., Davenport J.R., Croyle M.J., Haycraft C.J. and Yoder B.K. (2005). Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737(orpk) mutant mice. Lab Invest. 85:45–64

    PubMed  CAS  Google Scholar 

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Acknowledgements

The author thanks Kyle Vogan and Hiroshi Hamada for important comments on the views expressed in this perspective as well as for suggestions relating to the text, and Martin Blum for sharing data in advance of publication.

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Authors and Affiliations

  1. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA

    Cliff Tabin

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  1. Cliff Tabin
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Correspondence to Cliff Tabin.

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The University of Queensland Essay in Developmental Biology for 2005

The University of Queensland is proud to announce that its author for the 2005 Essay in Developmental Biology is Professor Cliff Tabin from Harvard University. This year the Editors of the Journal of Molecular Histology, Professor’s Brian Key and Ismo Virtanen, have kindly agreed to publish this esteemed essay. This essay is sponsored by the Developmental Biology Program in the Faculty of Biological and Chemical Sciences (http://www.bacs.uq.edu.au/) at the University of Queensland. The essay recognizes innovative thought in the field of Developmental Biology and is intended to both provoke and inspire our young scientists.

Cliff Tabin is a world-renown developmental biologist based in the Department of Genetics at the Harvard Medical School (http://genetics.med.harvard.edu/~tabin/). His research spans a variety of disciplines and exhibits considerable depth and insight into some of the most pertinent questions in the field. Cliff is a plenary lecturer at this year’s 15th International Society of Developmental Biologists Congress in Sydney, Australia.

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Tabin, C. Do we know anything about how left–right asymmetry is first established in the vertebrate embryo?. J Mol Hist 36, 317–323 (2005). https://doi.org/10.1007/s10735-005-9000-y

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  • DOI: https://doi.org/10.1007/s10735-005-9000-y

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