Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 02 2023
10 02 2023
Historique:
received:
26
06
2022
accepted:
27
01
2023
pubmed:
11
2
2023
medline:
15
2
2023
entrez:
10
2
2023
Statut:
epublish
Résumé
Cellular differentiation is directly determined by concentration gradients of morphogens. As a central model for gradient formation during development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in Drosophila wing and eye discs. What is not known is how extracellular Hh spread is achieved and how it translates into precise gradients. Here we show that two separate binding areas located on opposite sides of the Hh molecule can interact directly and simultaneously with two heparan sulfate (HS) chains to temporarily cross-link the chains. Mutated Hh lacking one fully functional binding site still binds HS but shows reduced HS cross-linking. This, in turn, impairs Hhs ability to switch between both chains in vitro and results in striking Hh gradient hypomorphs in vivo. The speed and propensity of direct Hh switching between HS therefore shapes the Hh gradient, revealing a scalable design principle in morphogen-patterned tissues.
Identifiants
pubmed: 36765094
doi: 10.1038/s41467-023-36450-y
pii: 10.1038/s41467-023-36450-y
pmc: PMC9918555
doi:
Substances chimiques
Drosophila Proteins
0
Hedgehog Proteins
0
Heparitin Sulfate
9050-30-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
758Informations de copyright
© 2023. The Author(s).
Références
Development. 1992 Aug;115(4):957-71
pubmed: 1280560
Dev Cell. 2002 Jun;2(6):785-96
pubmed: 12062090
Development. 2004 Apr;131(7):1563-75
pubmed: 14998928
Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):5869-74
pubmed: 20231458
Development. 2004 May;131(9):1927-38
pubmed: 15056609
Science. 2018 Aug 10;361(6402):
pubmed: 29954986
Nat Rev Genet. 2020 Nov;21(11):683-697
pubmed: 32778819
Dev Biol. 2022 Apr;484:12-21
pubmed: 35120908
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17026-31
pubmed: 16282375
Open Biol. 2015 Aug;5(8):
pubmed: 26269427
Adv Protein Chem Struct Biol. 2013;92:253-97
pubmed: 23954104
Nat Rev Genet. 2021 Jun;22(6):393-411
pubmed: 33767424
Biochem Biophys Res Commun. 1997 Aug 18;237(2):465-9
pubmed: 9268735
J Mol Biol. 1993 Dec 5;234(3):779-815
pubmed: 8254673
Nature. 2013 May 30;497(7451):628-32
pubmed: 23624372
Nature. 1998 Jul 2;394(6688):85-8
pubmed: 9665133
Development. 2018 Sep 21;145(18):
pubmed: 30242104
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W665-7
pubmed: 15215472
Dev Cell. 2008 May;14(5):712-25
pubmed: 18477454
Development. 2019 Apr 25;146(8):
pubmed: 30918051
Arteriosclerosis. 1989 Jan-Feb;9(1):21-32
pubmed: 2463827
J Biol Chem. 2011 Dec 30;286(52):44391-402
pubmed: 22049079
J Biol Chem. 2000 Apr 14;275(15):10995-1001
pubmed: 10753901
Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16420-5
pubmed: 24062467
Dev Cell. 2007 Jul;13(1):57-71
pubmed: 17609110
Dev Biol. 2011 Oct 1;358(1):168-80
pubmed: 21806980
Proc Natl Acad Sci U S A. 2010 Dec 7;107(49):21004-9
pubmed: 21078959
J Clin Invest. 2001 Jul;108(2):165-7
pubmed: 11457866
Science. 2007 May 25;316(5828):1191-4
pubmed: 17525339
Dev Cell. 2010 Apr 20;18(4):605-20
pubmed: 20412775
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17208-13
pubmed: 17077139
Elife. 2018 Mar 09;7:
pubmed: 29522397
Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5752-7
pubmed: 16585517
Science. 2013 Feb 22;339(6122):923-7
pubmed: 23430648
Nucleic Acids Res. 2003 Jul 1;31(13):3381-5
pubmed: 12824332
Development. 1996 Jun;122(6):1849-58
pubmed: 8674424
Cell. 2008 Jun 27;133(7):1214-27
pubmed: 18585355
Nat Cell Biol. 2013 Nov;15(11):1269-81
pubmed: 24121526
Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
pubmed: 11517324
PLoS Biol. 2009 Sep;7(9):e1000202
pubmed: 19787036
PLoS One. 2012;7(11):e48632
pubmed: 23152789
PLoS Biol. 2012 Jul;10(7):e1001361
pubmed: 22815649
J Mol Biol. 1970 Nov 14;53(3):401-17
pubmed: 4924006
Nat Struct Mol Biol. 2009 Jul;16(7):698-703
pubmed: 19561611
Trends Neurosci. 2001 May;24(5):251-4
pubmed: 11311363
Genetics. 2016 Aug;203(4):1613-28
pubmed: 27334272
J Chem Inf Model. 2018 Feb 26;58(2):315-327
pubmed: 29266929
J Biol Chem. 2009 Mar 20;284(12):8013-22
pubmed: 19176481
Sci Rep. 2022 Jun 29;12(1):10980
pubmed: 35768463
Methods. 2014 Jun 15;68(1):199-206
pubmed: 24556557
Mol Cell. 1999 Oct;4(4):633-9
pubmed: 10549295
Biochemistry. 1999 Nov 9;38(45):14868-80
pubmed: 10555969
Molecules. 2019 Apr 23;24(8):
pubmed: 31018591
Chem Commun (Camb). 2014 Dec 14;50(96):15148-51
pubmed: 25338834
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1885-90
pubmed: 12571364
Biomaterials. 2014 Oct;35(32):8903-15
pubmed: 25088726
Development. 2013 Apr;140(8):1621-38
pubmed: 23533171
Dev Biol. 2005 Aug 1;284(1):204-18
pubmed: 15963974
J Biol Chem. 2011 Jul 1;286(26):23608-19
pubmed: 21572042
Chem Sci. 2020 Mar 9;11(12):3307-3315
pubmed: 34122838
Curr Opin Genet Dev. 2007 Aug;17(4):264-71
pubmed: 17643982
Cold Spring Harb Perspect Biol. 2011 Jul 01;3(7):
pubmed: 21690215
Nat Rev Mol Cell Biol. 2005 Apr;6(4):306-17
pubmed: 15803137
Science. 2018 May 4;360(6388):543-548
pubmed: 29622726
Curr Biol. 1999 Jan 28;9(2):76-84
pubmed: 10021362
Nucleic Acids Res. 2008 Jul;36(12):4118-27
pubmed: 18544605
Development. 2004 Jan;131(1):73-82
pubmed: 14645127
Dev Biol. 2021 Aug;476:33-40
pubmed: 33775694
Cell. 1996 Jan 12;84(1):155-64
pubmed: 8548820
Genes Dev. 2001 Dec 1;15(23):3059-87
pubmed: 11731473
Development. 2002 May;129(9):2223-32
pubmed: 11959830
Protein Sci. 1993 Sep;2(9):1511-9
pubmed: 8401235
Trends Genet. 2004 Oct;20(10):498-505
pubmed: 15363904
Cell. 1993 Dec 3;75(5):927-38
pubmed: 8252628
Dev Biol. 2009 May 1;329(1):104-15
pubmed: 19268449
Development. 2013 Jan 1;140(1):82-92
pubmed: 23154412
Development. 2004 Feb;131(3):601-11
pubmed: 14729575
J Biol Chem. 1999 Feb 19;274(8):5236-44
pubmed: 9988774
Development. 2013 Dec;140(23):4818-25
pubmed: 24154526
J Biol Chem. 1999 May 28;274(22):15293-6
pubmed: 10336412
Nature. 2009 Sep 24;461(7263):533-6
pubmed: 19741606
Chem Commun (Camb). 2018 Jan 23;54(8):948-951
pubmed: 29319072
Nat Commun. 2014 Dec 04;5:5649
pubmed: 25472772
Nature. 1991 Sep 12;353(6340):184-7
pubmed: 1653906
Nat Commun. 2019 Sep 26;10(1):4390
pubmed: 31558728