title: A subpopulation of smooth muscle cells, derived from melanocyte-competent precursors, prevents patent ductus arteriosus.
abstract: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA), a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2) and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes.
authors: Developmental Genetics of Melanocytes, Institut Curie, Orsay, France.
authors: Ichiro
authors: I
authors: Yajima
authors: Sophie
authors: S
authors: Colombo
authors: Isabel
authors: I
authors: Puig
authors: Delphine
authors: D
authors: Champeval
authors: Mayuko
authors: M
authors: Kumasaka
authors: Elodie
authors: E
authors: Belloir
authors: Jacky
authors: J
authors: Bonaventure
authors: Manuel
authors: M
authors: Mark
authors: Hiroaki
authors: H
authors: Yamamoto
authors: Mark M
authors: MM
authors: Taketo
authors: Philippe
authors: P
authors: Choquet
authors: Heather C
authors: HC
authors: Etchevers
authors: Friedrich
authors: F
authors: Beermann
authors: Véronique
authors: V
authors: Delmas
authors: Laurent
authors: L
authors: Monassier
authors: Lionel
authors: L
authors: Larue
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D049109:Cell Proliferation; D004374:Ductus Arteriosus, Patent / Q000209:etiology / Q000503:physiopathology*; D047108:Embryonic Development; D005260:Female; D006801:Humans; D008544:Melanocytes / Q000166:cytology; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D011247:Pregnancy; D047928:Premature Birth / Q000503:physiopathology*; D060449:Wnt Signaling Pathway
references: Anat Rec A Discov Mol Cell Evol Biol. 2005 Aug;285(2):748-57
references: 15977222
references: J R Soc Interface. 2009 Nov 6;6(40):1097-102
references: 19586956
references: Zebrafish. 2006;3(4):455-63
references: 18377225
references: Dev Biol. 1997 Dec 1;192(1):99-107
references: 9405100
references: J Clin Invest. 2008 Feb;118(2):515-25
references: 18188448
references: Nat Genet. 1999 Jan;21(1):70-1
references: 9916792
references: Can J Physiol Pharmacol. 1973 Mar;51(3):220-5
references: 4705142
references: Oncogene. 2006 Dec 4;25(57):7482-91
references: 17143292
references: Ann Thorac Surg. 1984 Aug;38(2):146-50
references: 6465992
references: Pigment Cell Res. 2002 Dec;15(6):426-32
references: 12453184
references: Pigment Cell Res. 2007 Aug;20(4):305-6
references: 17630964
references: Circ Res. 1994 Nov;75(5):803-12
references: 7923625
references: Pigment Cell Melanoma Res. 2009 Jun;22(3):331-4
references: 19220779
references: J Clin Invest. 2009 Sep;119(9):2538-49
references: 19690384
references: Nat Med. 2002 Feb;8(2):91-2
references: 11821873
references: Nat Cell Biol. 2000 Jun;2(6):371-5
references: 10854329
references: Nucleic Acids Res. 2006;34(19):5705-14
references: 17040897
references: Physiol Rev. 1975 Jan;55(1):62-78
references: 1088992
references: C R Biol. 2007 Nov;330(11):821-7
references: 17923376
references: Nat Genet. 2006 Mar;38(3):343-9
references: 16444274
references: J Clin Invest. 2009 Nov;119(11):3420-36
references: 19855129
references: J Pediatr. 1983 Jun;102(6):895-906
references: 6343572
references: Circ Res. 1998 Feb 9;82(2):221-31
references: 9468193
references: Genesis. 2006 Jan;44(1):34-43
references: 16419042
references: Cell. 1993 Jul 30;74(2):395-404
references: 8343963
references: Circulation. 2006 Oct 24;114(17):1873-82
references: 17060397
references: J Clin Invest. 2009 Dec;119(12):3586-96
references: 19884655
references: Circ Res. 2006 Dec 8;99(12):1329-37
references: 17122440
references: Circulation. 2004 Aug 24;110(8):969-74
references: 15302781
references: Genes Dev. 2007 Nov 15;21(22):2923-35
references: 18006687
references: J Pediatr. 1978 Mar;92(3):467-73
references: 632994
references: Nat Med. 2006 Jun;12(6):699-704
references: 16732282
references: Dev Biol. 2006 Jun 15;294(2):292-302
references: 16643886
references: Nature. 1997 Nov 6;390(6655):78-81
references: 9363893
references: Pigment Cell Melanoma Res. 2008 Aug;21(4):464-70
references: 18444965
references: Nature. 1998 Nov 26;396(6709):370-3
references: 9845073
references: Circ Res. 2006 Jun 23;98(12):1547-54
references: 16709902
references: Dev Biol. 1999 Sep 15;213(2):418-31
references: 10479458
references: Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1059-64
references: 11158594
references: Nat Genet. 2000 May;25(1):42-6
references: 10802654
references: Anat Rec. 1993 Nov;237(3):385-99
references: 8291692
references: Genesis. 2003 Jun;36(2):73-80
references: 12820167
references: Biochem Biophys Res Commun. 1998 May 8;246(1):7-12
references: 9600059
references: Anat Embryol (Berl). 1999 Dec;200(6):559-71
references: 10592060
references: Am J Hum Genet. 1997 Sep;61(3):620-9
references: 9326327
references: Development. 1994 Aug;120(8):2103-11
references: 7925014
references: Development. 2000 Apr;127(8):1607-16
references: 10725237
references: J Clin Invest. 2006 Oct;116(10):2673-81
references: 16998588
references: Pigment Cell Res. 2002 Aug;15(4):305-9
references: 12100497
references: Science. 2004 Feb 13;303(5660):1020-3
references: 14716020
references: Nat Med. 2010 Jan;16(1):75-82
references: 19966813
references: Cancer Res. 2003 Feb 1;63(3):728-34
references: 12566320
references: Cell. 2001 Feb 23;104(4):619-29
references: 11239417
references: EMBO J. 1999 Nov 1;18(21):5931-42
references: 10545105
references: Development. 2001 Apr;128(8):1253-64
references: 11262227
references: Pigment Cell Melanoma Res. 2008 Aug;21(4):471-6
references: 18627529