The function and expansion of the Patched- and Hedgehog-related homologs in C. elegans
Reads0
Chats0
TLDR
A global survey of the phenotypes produced by RNAi reveals that these genes do not require Smo for activity and that they function in multiple aspects of C. elegans development, including molting, cytokinesis, growth, and pattern formation.Abstract:
The Hedgehog (Hh) signaling pathway promotes pattern formation and cell proliferation in Drosophila and vertebrates. Hh is a ligand that binds and represses the Patched (Ptc) receptor and thereby releases the latent activity of the multipass membrane protein Smoothened (Smo), which is essential for transducing the Hh signal. In Caenorhabditis elegans, the Hh signaling pathway has undergone considerable divergence. Surprisingly, obvious Smo and Hh homologs are absent whereas PTC, PTC-related (PTR), and a large family of nematode Hh-related (Hh-r) proteins are present. We find that the number of PTC-related and Hh-r proteins has expanded in C. elegans, and that this expansion occurred early in Nematoda. Moreover, the function of these proteins appears to be conserved in Caenorhabditis briggsae. Given our present understanding of the Hh signaling pathway, the absence of Hh and Smo raises many questions about the evolution and the function of the PTC, PTR, and Hh-r proteins in C. elegans. To gain insights into their roles, we performed a global survey of the phenotypes produced by RNA-mediated interference (RNAi). Our study reveals that these genes do not require Smo for activity and that they function in multiple aspects of C. elegans development, including molting, cytokinesis, growth, and pattern formation. Moreover, a subset of the PTC, PTR, and Hh-r proteins have the same RNAi phenotypes, indicating that they have the potential to participate in the same processes.read more
Citations
More filters
Journal ArticleDOI
The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans
TL;DR: It is shown that the membrane-bound V0 sector of the vacuolar H+-atPase (V-ATPase) acts in this pathway, independent of its contribution to the V-ATpase proton pump activity, and raised the possibility that the V 0 sector mediates exosome and morphogen release in mammals.
Journal ArticleDOI
Hedgehog signalling: emerging evidence for non-canonical pathways.
TL;DR: The aim of this review is to present the cumulative evidence supporting non-canonical HH signalling, with the hope of promoting further enquiry into this area.
Journal ArticleDOI
Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability.
Abdul Noor,Annabel Whibley,Christian R. Marshall,Peter J. Gianakopoulos,Amélie Piton,Andrew R. Carson,M Orlic-Milacic,Anath C. Lionel,Daisuke Sato,Dalila Pinto,Irene Drmic,Carolyn Noakes,Lili Senman,Xiaoyun Zhang,Rong Mo,Julie Gauthier,Jennifer Crosbie,Alistair T. Pagnamenta,Jeffrey Munson,Annette Estes,Andreas Fiebig,Andre Franke,Stefan Schreiber,Alexandre F.R. Stewart,Robert Roberts,Ruth McPherson,Stephen J. Guter,Edwin H. Cook,Geraldine Dawson,Gerard D. Schellenberg,Agatino Battaglia,Elena Maestrini,Linda Jeng,Terry Hutchison,Evica Rajcan-Separovic,Albert E. Chudley,Suzanne M E Lewis,Xudong Liu,Jeanette J. A. Holden,Bridget A. Fernandez,Lonnie Zwaigenbaum,Susan E. Bryson,Wendy Roberts,Peter Szatmari,Louise Gallagher,Michael R. Stratton,Jozef Gecz,Angela F. Brady,Charles E. Schwartz,Russell Schachar,Anthony P. Monaco,Guy A. Rouleau,Chi-chung Hui,F. Lucy Raymond,Stephen W. Scherer,John B. Vincent +55 more
TL;DR: Genetic analysis in thousands of patients and control subjects suggests that the PTCHD1 gene may be part of the Hedgehog signaling pathway, which is important in embryonic development, and suggests that this locus is involved in ~1% of individuals with ASD and intellectual disability.
Journal ArticleDOI
Extensive Oscillatory Gene Expression during C. elegans Larval Development
Gert-Jan Hendriks,Gert-Jan Hendriks,Dimos Gaidatzis,Dimos Gaidatzis,Florian Aeschimann,Florian Aeschimann,Helge Großhans +6 more
TL;DR: P pervasive, large-amplitude, and phase-locked oscillations of gene expression in developing C. elegans larvae, caused by periodic transcription, are reported and ribosome profiling reveals that periodic mRNA accumulation causes rhythmic translation, potentially facilitating transient protein accumulation as well as coordinated production of stable, complex structures such as the cuticle.
Journal ArticleDOI
TGF-β signaling in C. elegans.
TL;DR: Two of the ligands, DBL-1 and DAF-7, signal through a canonical receptor-Smad signaling pathway; while a third ligand, UNC-129, interacts with a noncanonical signaling pathway.
References
More filters
Journal ArticleDOI
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
Stephen F. Altschul,Thomas L. Madden,Alejandro A. Schäffer,Jinghui Zhang,Zheng Zhang,Webb Miller,David J. Lipman +6 more
TL;DR: A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original.
Journal ArticleDOI
The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools.
TL;DR: ClUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W, providing an integrated system for performing multiple sequence and profile alignments and analysing the results.
Journal ArticleDOI
Initial sequencing and analysis of the human genome.
Eric S. Lander,Lauren Linton,Bruce W. Birren,Chad Nusbaum,Michael C. Zody,Jennifer Baldwin,Keri Devon,Ken Dewar,Michael Doyle,William Fitzhugh,Roel Funke,Diane Gage,Katrina Harris,Andrew Heaford,John Howland,Lisa Kann,Jessica A. Lehoczky,Rosie Levine,Paul A. McEwan,Kevin McKernan,James Meldrim,Jill P. Mesirov,Cher Miranda,William Morris,Jerome Naylor,Christina Raymond,Mark Rosetti,Ralph Santos,Andrew Sheridan,Carrie Sougnez,Nicole Stange-Thomann,Nikola Stojanovic,Aravind Subramanian,Dudley Wyman,Jane Rogers,John Sulston,R Ainscough,Stephan Beck,David Bentley,John Burton,C M Clee,Nigel P. Carter,Alan Coulson,Rebecca Deadman,Panos Deloukas,Andrew Dunham,Ian Dunham,Richard Durbin,Lisa French,Darren Grafham,Simon G. Gregory,Tim Hubbard,Sean Humphray,Adrienne Hunt,Matthew Jones,Christine Lloyd,Amanda McMurray,Lucy Matthews,Simon Mercer,Sarah Milne,James C. Mullikin,Andrew J. Mungall,Robert W. Plumb,Mark T. Ross,Ratna Shownkeen,Sarah Sims,Robert H. Waterston,Richard K. Wilson,LaDeana W. Hillier,John Douglas Mcpherson,Marco A. Marra,Elaine R. Mardis,Lucinda Fulton,Asif T. Chinwalla,Kymberlie H. Pepin,Warren Gish,Stephanie L. Chissoe,Michael C. Wendl,Kim D. Delehaunty,Tracie L. Miner,Andrew Delehaunty,Jason B. Kramer,Lisa Cook,Robert S. Fulton,Douglas L. Johnson,Patrick Minx,Sandra W. Clifton,Trevor Hawkins,Elbert Branscomb,Paul Predki,Paul G. Richardson,Sarah Wenning,Tom Slezak,Norman A. Doggett,Jan Fang Cheng,Anne S. Olsen,Susan Lucas,Christopher J. Elkin,Edward Uberbacher,Marvin Frazier,Richard A. Gibbs,Donna M. Muzny,Steven E. Scherer,John Bouck,Erica Sodergren,Kim C. Worley,Catherine M. Rives,James H. Gorrell,Michael L. Metzker,Susan L. Naylor,Raju Kucherlapati,David L. Nelson,George M. Weinstock,Yoshiyuki Sakaki,Asao Fujiyama,Masahira Hattori,Tetsushi Yada,Atsushi Toyoda,Takehiko Itoh,Chiharu Kawagoe,Hidemi Watanabe,Yasushi Totoki,Todd D. Taylor,Jean Weissenbach,Roland Heilig,William Saurin,François Artiguenave,Philippe Brottier,Thomas Brüls,Eric Pelletier,Catherine Robert,Patrick Wincker,André Rosenthal,Matthias Platzer,Gerald Nyakatura,Stefan Taudien,Andreas Rump,Douglas R. Smith,Lynn Doucette-Stamm,Marc Rubenfield,Keith Weinstock,Mei Lee Hong,Joann Dubois,Huanming Yang,Jun Yu,Jian Wang,Guyang Huang,Jun Gu,Leroy Hood,Lee Rowen,Anup Madan,Shizen Qin,Ronald W. Davis,Nancy A. Federspiel,A. Pia Abola,Michael Proctor,Bruce A. Roe,Feng Chen,Huaqin Pan,Juliane Ramser,Hans Lehrach,Richard Reinhardt,W. Richard McCombie,Melissa De La Bastide,Neilay Dedhia,H. Blöcker,K. Hornischer,Gabriele Nordsiek,Richa Agarwala,L. Aravind,Jeffrey A. Bailey,Alex Bateman,Serafim Batzoglou,Ewan Birney,Peer Bork,Daniel G. Brown,Christopher B. Burge,Lorenzo Cerutti,Hsiu Chuan Chen,Deanna M. Church,Michele Clamp,Richard R. Copley,Tobias Doerks,Sean R. Eddy,Evan E. Eichler,Terrence S. Furey,James E. Galagan,James G. R. Gilbert,Cyrus L. Harmon,Yoshihide Hayashizaki,David Haussler,Henning Hermjakob,Karsten Hokamp,Wonhee Jang,L. Steven Johnson,Thomas A. Jones,Simon Kasif,Arek Kaspryzk,Scot Kennedy,W. James Kent,Paul Kitts,Eugene V. Koonin,Ian F Korf,David Kulp,Doron Lancet,Todd M. Lowe,Aoife McLysaght,Tarjei S. Mikkelsen,John V. Moran,Nicola Mulder,Victor J. Pollara,Chris P. Ponting,Greg Schuler,Jörg Schultz,Guy Slater,Arian F.A. Smit,Elia Stupka,Joseph Szustakowki,Danielle Thierry-Mieg,Jean Thierry-Mieg,Lukas Wagner,John W. Wallis,Raymond Wheeler,Alan Williams,Yuri I. Wolf,Kenneth H. Wolfe,Shiaw Pyng Yang,Ru Fang Yeh,Francis S. Collins,Mark S. Guyer,Jane Peterson,Adam Felsenfeld,Kris A. Wetterstrand,Richard M. Myers,Jeremy Schmutz,Mark Dickson,Jane Grimwood,David R. Cox,Maynard V. Olson,Rajinder Kaul,Christopher K. Raymond,Nobuyoshi Shimizu,Kazuhiko Kawasaki,Shinsei Minoshima,Glen A. Evans,Maria Athanasiou,Roger A. Schultz,Aristides Patrinos,Michael J. Morgan +248 more
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
The genetics of caenorhabditis elegans
TL;DR: In this paper, the authors describe methods for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm.
Journal ArticleDOI
TreeView : an application to display phylogenetic trees on personal computers
TL;DR: TreeView is a simple, easy to use phylogenetic tree viewing utility that runs under both MacOS (on Apple Macintosh computers) and under Microsoft Windows on Intel based computers, the two most common personal computers used by biologists.