دورية أكاديمية
Mechanism for generation of left isomerism in Ccdc40 mutant embryos.
| العنوان: | Mechanism for generation of left isomerism in Ccdc40 mutant embryos. |
|---|---|
| المؤلفون: | Sugrue KF; Institute for Biomedical Sciences, The George Washington University, Washington, DC, United States of America.; Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC, United States of America., Zohn IE; Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC, United States of America. |
| المصدر: | PloS one [PLoS One] 2017 Feb 09; Vol. 12 (2), pp. e0171180. Date of Electronic Publication: 2017 Feb 09 (Print Publication: 2017). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
| مواضيع طبية MeSH: | Gene Expression Regulation, Developmental* , Mutation*, Body Patterning/*genetics , Proteins/*genetics, Animals ; Cilia/metabolism ; Cilia/pathology ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Left-Right Determination Factors/genetics ; Left-Right Determination Factors/metabolism ; Mesoderm/metabolism ; Mice ; Nodal Protein/genetics ; Nodal Protein/metabolism ; Proteins/metabolism |
| مستخلص: | Leftward fluid flow in the mouse node is generated by cilia and is critical for initiating asymmetry of the left-right axis. Coiled-coil domain containing-40 (Ccdc40) plays an evolutionarily conserved role in the assembly of motile cilia and establishment of the left-right axis. Approximately one-third of Ccdc40lnks mutant embryos display situs defects and here we investigate the underlying mechanism. Ccdc40lnks mutants show delayed induction of markers of the left-lateral plate mesoderm (L-LPM) including Lefty1, Lefty2 and Nodal. Consistent with defective cilia motility compromising fluid flow across the node, initiation of asymmetric perinodal Cerberus like-2 (Cerl2) expression is delayed and then randomized. This is followed by delayed and then randomized asymmetric Nodal expression around the node. We propose a model to explain how left isomerism arises in a proportion of Ccdc40lnks mutants. We postulate that with defective motile cilia, Cerl2 expression remains symmetric and Nodal is antagonized equally on both sides of the node. This effectively reduces Nodal activation bilaterally, leading to reduced and delayed activation of Nodal and its antagonists in the LPM. This model is further supported by the failure to establish Nodal expression in the left-LPM with reduced Nodal gene dosage in Ccdc40lnks/lnks;NodalLacZ/+ mutants causing a predominance of right not left isomerism. Together these results suggest a model where cilia generated fluid flow in the node functions to ensure robust Nodal activation and a timely left-sided developmental program in the LPM. Competing Interests: The authors have declared that no competing interests exist. |
| References: | J Cell Biol. 1999 May 17;145(4):825-36. (PMID: 10330409) Nat Genet. 2011 Jan;43(1):72-8. (PMID: 21131972) Nature. 2002 Jul 4;418(6893):96-9. (PMID: 12097914) Circulation. 2007 Jun 5;115(22):2793-5. (PMID: 17548739) Nat Genet. 1998 Sep;20(1):54-7. (PMID: 9731531) Mol Cell. 2000 Jan;5(1):35-47. (PMID: 10678167) Eur J Med Genet. 2006 Sep-Oct;49(5):349-62. (PMID: 16461029) Dev Biol. 2003 Apr 1;256(1):160-72. (PMID: 12654299) Dev Cell. 2006 Oct;11(4):495-504. (PMID: 17011489) Hum Mutat. 2013 Mar;34(3):462-72. (PMID: 23255504) Hum Mol Genet. 1998;7(10):1565-71. (PMID: 9735377) Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11325-30. (PMID: 16061793) Nature. 1991 Sep 26;353(6342):348-51. (PMID: 1922339) Dev Biol. 2005 Jun 1;282(1):1-13. (PMID: 15936325) Mol Cell. 1999 Oct;4(4):459-68. (PMID: 10549278) Development. 2001 May;128(10):1831-43. (PMID: 11311163) Nat Rev Genet. 2006 Apr;7(4):283-93. (PMID: 16543932) Nature. 1996 May 9;381(6578):155-8. (PMID: 8610012) Mech Dev. 1998 Jul;75(1-2):107-15. (PMID: 9739117) Development. 2000 Jun;127(11):2347-55. (PMID: 10804177) Development. 2007 Nov;134(21):3893-904. (PMID: 17913787) Development. 2006 Jan;133(1):3-14. (PMID: 16339192) J Cell Sci. 2014 Jun 1;127(Pt 11):2407-19. (PMID: 24681783) Dev Biol. 2013 Aug 15;380(2):222-32. (PMID: 23707899) J Med Genet. 2012 Jun;49(6):410-6. (PMID: 22693285) Development. 2003 Jan;130(1):3-13. (PMID: 12441287) Nat Rev Genet. 2010 May;11(5):331-44. (PMID: 20395968) Nat Commun. 2012 Jan 10;3:622. (PMID: 22233632) Nat Rev Neurosci. 2003 Apr;4(4):289-97. (PMID: 12671645) Development. 1999 Dec;126(23):5495-504. (PMID: 10556073) F1000Prime Rep. 2015 Mar 10;7:36. (PMID: 25926987) Dev Biol. 2005 Dec 1;288(1):1-20. (PMID: 16289136) Science. 2012 Oct 12;338(6104):226-31. (PMID: 22983710) Genes Cells. 1997 Aug;2(8):513-24. (PMID: 9348041) Cell. 1998 Aug 7;94(3):287-97. (PMID: 9708731) Nat Genet. 1998 Sep;20(1):58-61. (PMID: 9731532) Dev Biol. 2008 Feb 15;314(2):261-75. (PMID: 18178183) Annu Rev Cell Dev Biol. 2007;23:345-73. (PMID: 17506691) Dev Biol. 2012 Jul 1;367(1):15-24. (PMID: 22554696) Nature. 2003 Nov 6;426(6962):83-7. (PMID: 14603322) Nat Rev Mol Cell Biol. 2007 Nov;8(11):880-93. (PMID: 17955020) Genes Dev. 2002 Sep 15;16(18):2339-44. (PMID: 12231623) Nat Commun. 2012;3:1322. (PMID: 23271656) Dev Dyn. 2002 Jul;224(3):279-90. (PMID: 12112458) Development. 2002 Jul;129(14):3455-68. (PMID: 12091315) Dev Biol. 2011 May 15;353(2):321-30. (PMID: 21419113) Cell. 1993 Dec 31;75(7):1417-30. (PMID: 7916661) Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11376-81. (PMID: 10500184) Nat Genet. 2011 Jan;43(1):79-84. (PMID: 21131974) Annu Rev Physiol. 2007;69:377-400. (PMID: 17009929) Cell. 2006 May 5;125(3):439-42. (PMID: 16678091) Dev Cell. 2001 Jul;1(1):127-38. (PMID: 11703930) Curr Top Dev Biol. 2008;85:151-74. (PMID: 19147005) Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):307-17. (PMID: 19876930) Nat Rev Genet. 2002 Feb;3(2):103-13. (PMID: 11836504) Genes Dev. 2003 May 15;17(10):1213-8. (PMID: 12730123) Development. 2009 Dec;136(23):3917-25. (PMID: 19906859) Genes Dev. 2003 May 15;17(10):1207-12. (PMID: 12730124) Cell. 2006 Jun 2;125(5):957-69. (PMID: 16751104) Development. 2003 May;130(9):1795-804. (PMID: 12642485) Cell. 1998 Dec 11;95(6):829-37. (PMID: 9865700) Genes Dev. 2004 Oct 1;18(19):2342-7. (PMID: 15466485) Cell. 2011 Jun 24;145(7):1129-41. (PMID: 21703454) Am J Med Genet. 2001 Jul 15;101(4):345-55. (PMID: 11471158) Cilia. 2015 Jan 14;4(1):1. (PMID: 25589952) Development. 2010 Nov;137(21):3625-32. (PMID: 20876649) Dev Dyn. 2001 Oct;222(2):301-7. (PMID: 11668607) N Engl J Med. 2011 Apr 21;364(16):1533-43. (PMID: 21506742) Genes Dev. 1997 Jul 15;11(14):1812-26. (PMID: 9242489) |
| معلومات مُعتمدة: | U54 HD090257 United States HD NICHD NIH HHS |
| المشرفين على المادة: | 0 (CCDC40 protein, mouse) 0 (Dte protein, mouse) 0 (Intercellular Signaling Peptides and Proteins) 0 (Left-Right Determination Factors) 0 (Lefty1 protein, mouse) 0 (Lefty2 protein, mouse) 0 (Nodal Protein) 0 (Nodal protein, mouse) 0 (Proteins) |
| تواريخ الأحداث: | Date Created: 20170210 Date Completed: 20170815 Latest Revision: 20181113 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC5300185 |
| DOI: | 10.1371/journal.pone.0171180 |
| PMID: | 28182636 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1932-6203 |
|---|---|
| DOI: | 10.1371/journal.pone.0171180 |