- Source:
Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
- Publication Information:
Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
- Subject Terms:
- Abstract:
Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. The cytoneme morphogen transport model posits that specialized filopodia extend between morphogen-sending and responding cells to ensure that appropriate signaling thresholds are achieved. How morphogens are transported along and deployed from cytonemes, how quickly a cytoneme-delivered, receptor-dependent signal is initiated, and whether these processes are conserved across phyla are not known. Herein, we reveal that the actin motor Myosin 10 promotes vesicular transport of Sonic Hedgehog (SHH) morphogen in mouse cell cytonemes, and that SHH morphogen gradient organization is altered in neural tubes of Myo10 -/- mice. We demonstrate that cytoneme-mediated deposition of SHH onto receiving cells induces a rapid, receptor-dependent signal response that occurs within seconds of ligand delivery. This activity is dependent upon a novel Dispatched (DISP)-BOC/CDON co-receptor complex that functions in ligand-producing cells to promote cytoneme occurrence and facilitate ligand delivery for signal activation.
Competing Interests: EH, MD, DS, YZ, BW, RL, SP, AS, JT, RC, MM, CR, SO No competing interests declared
(© 2021, Hall et al.)
- References:
J Biol Chem. 2012 Dec 21;287(52):43708-19. (PMID: 23118222)
Biochem J. 1994 Jun 15;300 ( Pt 3):665-72. (PMID: 8010948)
Cell Rep. 2012 Aug 30;2(2):308-20. (PMID: 22902404)
Nat Commun. 2014 Jul 08;5:4272. (PMID: 25001599)
Nat Cell Biol. 2004 Jun;6(6):523-31. (PMID: 15156152)
Development. 2011 Jan;138(1):75-85. (PMID: 21115611)
Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6548-53. (PMID: 16611729)
Development. 2014 Feb;141(4):729-36. (PMID: 24496611)
Cell. 1999 May 28;97(5):599-607. (PMID: 10367889)
Dev Cell. 2016 Mar 21;36(6):639-53. (PMID: 26972603)
Dev Cell. 2015 Feb 9;32(3):290-303. (PMID: 25619925)
Nat Rev Mol Cell Biol. 2013 Jul;14(7):416-29. (PMID: 23719536)
Genes Dev. 2007 May 15;21(10):1244-57. (PMID: 17504941)
Science. 2014 Feb 21;343(6173):1244624. (PMID: 24385607)
Cell. 2006 Apr 21;125(2):343-57. (PMID: 16630821)
Trends Pharmacol Sci. 2016 Jan;37(1):62-72. (PMID: 26432668)
PLoS One. 2012;7(8):e42791. (PMID: 22912738)
Dev Biol. 1994 Apr;162(2):402-13. (PMID: 8150204)
Nature. 2013 May 30;497(7451):628-32. (PMID: 23624372)
Wiley Interdiscip Rev Dev Biol. 2014 Nov-Dec;3(6):445-63. (PMID: 25186102)
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4482-7. (PMID: 21368195)
J Biol Chem. 2019 Nov 1;294(44):16034-16048. (PMID: 31506300)
Nature. 1996 Nov 14;384(6605):176-9. (PMID: 8906794)
J Biol Chem. 1998 May 29;273(22):14037-45. (PMID: 9593755)
Dev Cell. 2006 May;10(5):647-56. (PMID: 16647304)
Biochem Biophys Res Commun. 2004 Jun 18;319(1):214-20. (PMID: 15158464)
Nature. 2006 Nov 16;444(7117):369-73. (PMID: 17086203)
Development. 2017 Sep 1;144(17):3134-3144. (PMID: 28743798)
Development. 2000 Apr;127(8):1593-605. (PMID: 10725236)
Cell. 2002 Oct 4;111(1):63-75. (PMID: 12372301)
Sci Rep. 2019 Jan 24;9(1):597. (PMID: 30679680)
Development. 2017 Feb 15;144(4):552-566. (PMID: 28196803)
Sci Rep. 2017 Dec 11;7(1):17354. (PMID: 29229982)
PLoS One. 2018 Aug 27;13(8):e0203170. (PMID: 30148884)
Dev Cell. 2007 Jul;13(1):57-71. (PMID: 17609110)
J Biol Chem. 1999 Apr 23;274(17):12049-54. (PMID: 10207028)
Hum Mol Genet. 2009 May 15;18(10):1719-39. (PMID: 19223390)
Nature. 2001 Jun 7;411(6838):716-20. (PMID: 11395778)
Dev Cell. 2011 Jun 14;20(6):775-87. (PMID: 21664576)
PLoS Biol. 2018 Jul 3;16(7):e2005970. (PMID: 29969450)
Genes Dev. 2012 Jun 15;26(12):1312-25. (PMID: 22677548)
Trends Cell Biol. 2019 May;29(5):385-395. (PMID: 30852081)
Development. 2008 Mar;135(6):1097-106. (PMID: 18272593)
Nat Cell Biol. 2013 Nov;15(11):1269-81. (PMID: 24121526)
Cell Rep. 2017 Jun 6;19(10):2074-2087. (PMID: 28591579)
Nat Protoc. 2015 May;10(5):660-80. (PMID: 25837418)
Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8320-5. (PMID: 26100903)
Science. 2018 Aug 10;361(6402):. (PMID: 29954986)
Elife. 2018 Jan 23;7:. (PMID: 29359685)
Cell Rep. 2018 Jul 24;24(4):973-986.e8. (PMID: 30044992)
Front Immunol. 2014 Sep 16;5:442. (PMID: 25278937)
Nat Cell Biol. 2002 Mar;4(3):246-50. (PMID: 11854753)
Cell Signal. 2017 Jan;30:30-40. (PMID: 27871935)
J Vis Exp. 2011 Aug 19;(54):. (PMID: 21876526)
Dev Cell. 2020 Nov 23;55(4):450-467.e8. (PMID: 33038332)
Cell. 1999 Dec 23;99(7):803-15. (PMID: 10619433)
Genes Dev. 2010 Jan 1;24(1):57-71. (PMID: 20048000)
Nature. 2005 Oct 13;437(7061):1018-21. (PMID: 16136078)
Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12591-8. (PMID: 21690386)
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12411-6. (PMID: 16894163)
Curr Biol. 2019 Jan 21;29(2):202-216.e7. (PMID: 30639111)
J Biol Chem. 2001 Sep 7;276(36):34348-54. (PMID: 11457842)
Sci Rep. 2019 Mar 12;9(1):4194. (PMID: 30862905)
EMBO J. 2011 Jun 03;30(13):2734-47. (PMID: 21642953)
Curr Biol. 2002 Sep 17;12(18):1628-32. (PMID: 12372258)
Development. 2017 Oct 1;144(19):3612-3624. (PMID: 28827391)
J Vis Exp. 2012 Jun 21;(64):. (PMID: 22760161)
Elife. 2017 Aug 21;6:. (PMID: 28825565)
Sci Signal. 2015 Jun 02;8(379):ra55. (PMID: 26038600)
J Biol Chem. 2006 Feb 17;281(7):4087-93. (PMID: 16339763)
Int J Dev Biol. 2018;62(1-2-3):225-234. (PMID: 29616731)
J Biol Chem. 2010 Jan 22;285(4):2562-8. (PMID: 19920144)
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3196-201. (PMID: 19218434)
Dev Cell. 2018 May 21;45(4):512-525.e5. (PMID: 29754802)
Science. 1996 Oct 11;274(5285):255-9. (PMID: 8824192)
Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3572-7. (PMID: 21321230)
Bio Protoc. 2018 Jul 5;8(13):. (PMID: 30906805)
Sci Rep. 2018 Jan 17;8(1):888. (PMID: 29343825)
J Cell Sci. 2011 Nov 15;124(Pt 22):3733-41. (PMID: 22124140)
Nat Commun. 2014 Dec 04;5:5649. (PMID: 25472772)
Curr Opin Genet Dev. 2014 Aug;27:67-73. (PMID: 24907447)
- Grant Information:
R35 GM122546 United States GM NIGMS NIH HHS; P30 CA021765 United States CA NCI NIH HHS; R01 GM134531 United States GM NIGMS NIH HHS
- Contributed Indexing:
Keywords: Cytoneme; cell biology; developmental biology; morphogen; mouse; myosin; signal transduction; sonic hedgehog
Local Abstract: [plain-language-summary] During development, cells must work together and talk to each other to build the organs and tissues of the growing embryo. To communicate precisely with long-distance targets, cells can project a series of thin finger-like structures known as cytonemes. Cells use these miniature highways to exchange cargo and signals, such as the protein sonic hedgehog (SHH for short). Alterations to the way SHH is exchanged during development predispose to cancer and lead to disorders of the nervous system. Yet, the mechanisms by which cytonemes work in mammals remain to be fully elucidated. In particular, it is still unclear how the structures start to form, and how the proteins are loaded and transported from one end to another. A ‘molecular motor’ called myosin 10, which can carry cargo along the internal skeleton of cells, may be involved in these processes. To find out, Hall et al. used fluorescent probes to track both myosin 10 and SHH in mouse cells, showing that myosin 10 carries SHH from the core of the signal-producing cell to the tips of cytonemes. There, the protein is passed to the target cell upon contact, triggering a quick response. SHH also appeared to be more than just passive cargo, interacting with another group of proteins in the signal-emitting cell before reaching its target. This mechanism then encourages the signalling cells to produce more cytonemes towards their neighbours. SHH is crucial during development, but also after birth: in fact, changes to SHH transport in adulthood can also disrupt tissue balance and hinder healing. Understanding how healthy tissues send this signal may reveal why and how disease emerges.
- Accession Number:
0 (Boc protein, mouse)
0 (Cdon protein, mouse)
0 (Cell Adhesion Molecules)
0 (Hedgehog Proteins)
0 (Immunoglobulin G)
0 (Ligands)
0 (Membrane Proteins)
0 (Myo10 protein, mouse)
0 (Receptors, Cell Surface)
0 (Shh protein, mouse)
0 (dispatched protein, mouse)
EC 3.6.4.1 (Myosins)
- Publication Date:
Date Created: 20210211 Date Completed: 20220128 Latest Revision: 20220128
- Publication Date:
20240829
- Accession Number:
PMC7968926
- Accession Number:
10.7554/eLife.61432
- Accession Number:
33570491
Processing Request
No Comments.