|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 126, Issue 23 5495-5504, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
DM Supp, M Brueckner, MR Kuehn, DP Witte, LA Lowe, J McGrath, J Corrales and SS Potter
Divisions of Molecular and Developmental Biology, The Children's Hospital Research Foundation, Cincinnati, Ohio, USA.
Vertebrates develop distinct asymmetries along the left-right axis, which are consistently aligned with the anteroposterior and dorsoventral axes. The mechanisms that direct this handed development of left-right asymmetries have been elusive, but recent studies of mutations that affect left-right development have shed light on the molecules involved. One molecule implicated in left-right specification is left-right dynein (LRD), a microtubule-based motor protein. In the LRD protein of the inversus viscerum (iv) mouse, there is a single amino acid difference at a conserved position, and the lrd gene is one of many genes deleted in the legless (lgl) mutation. Both iv and lgl mice display randomized left-right development. Here we extend the analysis of the lrd gene at the levels of sequence, expression and function. The complete coding sequence of the lrd gene confirms its classification as an axonemal, or ciliary, dynein. Expression of lrd in the node at embryonic day 7.5 is shown to be symmetric. At embryonic day 8.0, however, a striking asymmetric expression pattern is observed in all three germ layers of the developing headfold, suggesting roles in both the establishment and maintenance of left-right asymmetries. At later times, expression of lrd is also observed in the developing floorplate, gut and limbs. These results suggest function for LRD protein in both ciliated and non-ciliated cells, despite its sequence classification as axonemal. In addition, a targeted mutation of lrd was generated that deletes the part of the protein required for ATP binding, and hence motor function. The resulting left-right phenotype, randomization of laterality, is identical to that of iv and lgl mutants. Gross defects in ciliary structure were not observed in lrd/lrd mutants. Strikingly, however, the monocilia on mutant embryonic node cells were immotile. These results prove the identity of the iv and lrd genes. Further, they argue that LRD motor function, and resulting nodal monocilia movement, are required for normal left-right development.
This article has been cited by other articles:
|
|
 |
|
  M. K. Tayeh, H.-J. Yen, J. S. Beck, C. C. Searby, T. A. Westfall, H. Griesbach, V. C. Sheffield, and D. C. Slusarski Genetic interaction between Bardet-Biedl syndrome genes and implications for limb patterning Hum. Mol. Genet., July 1, 2008; 17(13): 1956 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Schneider, D. W. Houston, M. R. Rebagliati, and D. C. Slusarski Calcium fluxes in dorsal forerunner cells antagonize -catenin and alter left-right patterning Development, January 1, 2008; 135(1): 75 - 84. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Sarmah, V. P. Winfrey, G. E. Olson, B. Appel, and S. R. Wente A role for the inositol kinase Ipk1 in ciliary beating and length maintenance PNAS, December 11, 2007; 104(50): 19843 - 19848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Livraghi and S. H. Randell Cystic Fibrosis and Other Respiratory Diseases of Impaired Mucus Clearance Toxicol Pathol, January 1, 2007; 35(1): 116 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Bisgrove and H. J. Yost The roles of cilia in developmental disorders and disease Development, November 1, 2006; 133(21): 4131 - 4143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Shiratori and H. Hamada The left-right axis in the mouse: from origin to morphology Development, June 1, 2006; 133(11): 2095 - 2104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Yen, M. K. Tayeh, R. F. Mullins, E. M. Stone, V. C. Sheffield, and D. C. Slusarski Bardet-Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function Hum. Mol. Genet., March 1, 2006; 15(5): 667 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-a. Nakaya, K. Biris, T. Tsukiyama, S. Jaime, J. A. Rawls, and T. P. Yamaguchi Wnt3alinks left-right determination with segmentation and anteroposterior axis elongation Development, December 15, 2005; 132(24): 5425 - 5436. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Weninger, K. L. Floro, M. B. Bennett, S. L. Withington, J. I. Preis, J. P. M. Barbera, T. J. Mohun, and S. L. Dunwoodie Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development Development, March 15, 2005; 132(6): 1337 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Essner, J. D. Amack, M. K. Nyholm, E. B. Harris, and H. J. Yost 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, March 15, 2005; 132(6): 1247 - 1260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Rana, J. P. M. Barbera, T. A. Rodriguez, D. Lynch, E. Hirst, J. C. Smith, and R. S. P. Beddington Targeted deletion of the novel cytoplasmic dynein mD2LIC disrupts the embryonic organiser, formation of the body axes and specification of ventral cell fates Development, October 15, 2004; 131(20): 4999 - 5007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Marques, A. C. Borges, A. C. Silva, S. Freitas, M. Cordenonsi, and J. A. Belo The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis Genes & Dev., October 1, 2004; 18(19): 2342 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Levin THE EMBRYONIC ORIGINS OF LEFT-RIGHT ASYMMETRY Crit. Rev. Oral. Biol. Med., July 1, 2004; 15(4): 197 - 206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bonnafe, M. Touka, A. AitLounis, D. Baas, E. Barras, C. Ucla, A. Moreau, F. Flamant, R. Dubruille, P. Couble, et al. The Transcription Factor RFX3 Directs Nodal Cilium Development and Left-Right Asymmetry Specification Mol. Cell. Biol., May 15, 2004; 24(10): 4417 - 4427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Bell, C. M. Schreiner, R. R. Waclaw, K. Campbell, S. S. Potter, and W. J. Scott From the Cover: Sp8 is crucial for limb outgrowth and neuropore closure PNAS, October 14, 2003; 100(21): 12195 - 12200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Watanabe, Y. Saijoh, S. Nonaka, G. Sasaki, Y. Ikawa, T. Yokoyama, and H. Hamada The left-right determinant Inversin is a component of node monocilia and other 9+0 cilia Development, May 1, 2003; 130(9): 1725 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Ibanez-Tallon, N. Heintz, and H. Omran To beat or not to beat: roles of cilia in development and disease Hum. Mol. Genet., April 2, 2003; 12(90001): R27 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Tabin and K. J. Vogan A two-cilia model for vertebrate left-right axis specification Genes & Dev., January 1, 2003; 17(1): 1 - 6. [Full Text] [PDF]
|
|
|
|
|
|
D. Morgan, L. Eley, J. Sayer, T. Strachan, L. M. Yates, A. S. Craighead, and J. A. Goodship Expression analyses and interaction with the anaphase promoting complex protein Apc2 suggest a role for inversin in primary cilia and involvement in the cell cycle Hum. Mol. Genet., December 15, 2002; 11(26): 3345 - 3350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bartoloni, J.-L. Blouin, Y. Pan, C. Gehrig, A. K. Maiti, N. Scamuffa, C. Rossier, M. Jorissen, M. Armengot, M. Meeks, et al. Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia PNAS, August 6, 2002; 99(16): 10282 - 10286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Neesen, R. Kirschner, M. Ochs, A. Schmiedl, B. Habermann, C. Mueller, A. F. Holstein, T. Nuesslein, I. Adham, and W. Engel Disruption of an inner arm dynein heavy chain gene results in asthenozoospermia and reduced ciliary beat frequency Hum. Mol. Genet., May 1, 2001; 10(11): 1117 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Taulman, C. J. Haycraft, D. F. Balkovetz, and B. K. Yoder Polaris, a Protein Involved in Left-Right Axis Patterning, Localizes to Basal Bodies and Cilia Mol. Biol. Cell, March 1, 2001; 12(3): 589 - 599. [Abstract] [Full Text]
|
|
|
|
|
|
G. Rupp, E. O'Toole, and M. E. Porter The Chlamydomonas PF6 Locus Encodes a Large Alanine/Proline-Rich Polypeptide That Is Required for Assembly of a Central Pair Projection and Regulates Flagellar Motility Mol. Biol. Cell, March 1, 2001; 12(3): 739 - 751. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. A. Spencer, S. Eliazer, R. L. Ilaria , Jr., J. A. Richardson, and E. N. Olson Regulation of Microtubule Dynamics and Myogenic Differentiation by MURF, a Striated Muscle RING-Finger Protein J. Cell Biol., August 21, 2000; 150(4): 771 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Burdine and A. F. Schier Conserved and divergent mechanisms in left-right axis formation Genes & Dev., April 1, 2000; 14(7): 763 - 776. [Full Text]
|
|
|
|
 |
|
 S. King AAA domains and organization of the dynein motor unit J. Cell Sci., January 7, 2000; 113(14): 2521 - 2526. [Abstract] [PDF]
|
|
