title: Proliferation and cell cycle dynamics in the developing stellate ganglion.
abstract: Cell proliferation during nervous system development is poorly understood outside the mouse neocortex. We measured cell cycle dynamics in the embryonic mouse sympathetic stellate ganglion, where neuroblasts continue to proliferate following neuronal differentiation. At embryonic day (E) 9.5, when neural crest-derived cells were migrating and coalescing into the ganglion primordium, all cells were cycling, cell cycle length was only 10.6 h, and S-phase comprised over 65% of the cell cycle; these values are similar to those previously reported for embryonic stem cells. At E10.5, Sox10(+) cells lengthened their cell cycle to 38 h and reduced the length of S-phase. As cells started to express the neuronal markers Tuj1 and tyrosine hydroxylase (TH) at E10.5, they exited the cell cycle. At E11.5, when >80% of cells in the ganglion were Tuj1(+)/TH(+) neuroblasts, all cells were again cycling. Neuroblast cell cycle length did not change significantly after E11.5, and 98% of Sox10(-)/TH(+) cells had exited the cell cycle by E18.5. The cell cycle length of Sox10(+)/TH(-) cells increased during late embryonic development, and ∼25% were still cycling at E18.5. Loss of Ret increased neuroblast cell cycle length at E16.5 and decreased the number of neuroblasts at E18.5. A mathematical model generated from our data successfully predicted the relative change in proportions of neuroblasts and non-neuroblasts in wild-type mice. Our results show that, like other neurons, sympathetic neuron differentiation is associated with exit from the cell cycle; sympathetic neurons are unusual in that they then re-enter the cell cycle before later permanently exiting.
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Victoria 3010, Australia.
authors.forename: David G
authors.initials: DG
authors.lastname: Gonsalvez
authors.forename: Kylie N
authors.initials: KN
authors.lastname: Cane
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Landman
authors.forename: Hideki
authors.initials: H
authors.lastname: Enomoto
authors.forename: Heather M
authors.initials: HM
authors.lastname: Young
authors.forename: Colin R
authors.initials: CR
authors.lastname: Anderson
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D010671:Phenylurea Compounds / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000378:metabolism; D013233:Stellate Ganglion / Q000166:cytology* / Q000196:embryology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; C109220:NBPhox protein; D010671:Phenylurea Compounds; D055757:SOXE Transcription Factors; C527925:Sox10 protein, rat; D014157:Transcription Factors; D014404:Tubulin; C462941:beta3 tubulin, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C032766:ethylene diurea; D014446:Tyrosine 3-Monooxygenase; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse; D001973:Bromodeoxyuridine
references.citation: Cell Tissue Res. 2008 Sep;333(3):353-71
references.pmid: 18629541
references.citation: Dev Dyn. 2010 Mar;239(3):897-904
references.pmid: 20131352
references.citation: Nat Rev Genet. 2008 Feb;9(2):115-28
references.pmid: 18202695
references.citation: J Neurosci. 1996 Oct 1;16(19):6208-18
references.pmid: 8815902
references.citation: Dev Neurosci. 2000;22(1-2):44-55
references.pmid: 10657697
references.citation: Development. 2012 Mar;139(6):1095-104
references.pmid: 22318230
references.citation: J Neurosci. 1987 Nov;7(11):3739-48
references.pmid: 3681410
references.citation: Dev Biol. 2007 Jul 1;307(1):92-104
references.pmid: 17524389
references.citation: J Comp Neurol. 2008 Jun 20;508(6):867-78
references.pmid: 18399538
references.citation: Results Probl Cell Differ. 2002;39:1-25
references.pmid: 12353465
references.citation: Neuron. 1999 Aug;23(4):725-36
references.pmid: 10482239
references.citation: Dev Dyn. 2008 Apr;237(4):1119-32
references.pmid: 18351668
references.citation: Glia. 2008 Oct;56(13):1428-37
references.pmid: 18551627
references.citation: Curr Top Dev Biol. 2011;94:77-127
references.pmid: 21295685
references.citation: Eur J Neurosci. 2011 Nov;34(10):1563-73
references.pmid: 22103414
references.citation: J Neurocytol. 1976 Jun;5(3):351-60
references.pmid: 939968
references.citation: Cell Tissue Res. 2006 Jan;323(1):11-25
references.pmid: 16133146
references.citation: Development. 2011 Nov;138(21):4789-800
references.pmid: 21989918
references.citation: Oncogene. 2010 Mar 18;29(11):1566-79
references.pmid: 20101209
references.citation: Proc Natl Acad Sci U S A. 1980 Oct;77(10):6221-5
references.pmid: 6108565
references.citation: Curr Opin Neurobiol. 2003 Feb;13(1):26-33
references.pmid: 12593979
references.citation: Trends Cell Biol. 2010 May;20(5):233-43
references.pmid: 20153966
references.citation: Cell Stem Cell. 2009 Aug 7;5(2):141-9
references.pmid: 19664987
references.citation: Neuron. 2002 Jul 18;35(2):267-82
references.pmid: 12160745
references.citation: J Neurosci. 1995 Sep;15(9):6046-57
references.pmid: 7666188
references.citation: J Clin Invest. 2012 Sep;122(9):3145-58
references.pmid: 22922260
references.citation: Brain Res Dev Brain Res. 2002 Mar 31;134(1-2):77-85
references.pmid: 11947938
references.citation: Dev Neurosci. 1997;19(1):17-22
references.pmid: 9078427
references.citation: Development. 2001 Oct;128(20):3963-74
references.pmid: 11641220
references.citation: Nat Rev Neurosci. 2005 Sep;6(9):671-82
references.pmid: 16136171
references.citation: Nat Commun. 2011 Jan 11;2:154
references.pmid: 21224845
references.citation: J Neurocytol. 1989 Jun;18(3):311-8
references.pmid: 2746304
references.citation: Cereb Cortex. 2003 Jun;13(6):592-8
references.pmid: 12764033
references.citation: Dev Dyn. 1995 Oct;204(2):192-201
references.pmid: 8589443
references.citation: J Neurosci. 1998 Jan 1;18(1):237-50
references.pmid: 9412504
references.citation: Dev Biol. 1999 Jun 15;210(2):411-27
references.pmid: 10357900
references.citation: Development. 1997 Oct;124(20):4065-75
references.pmid: 9374403
references.citation: Neuron. 1998 Aug;21(2):317-24
references.pmid: 9728913
references.citation: Dev Biol. 2012 Sep 15;369(2):277-85
references.pmid: 22790009
references.citation: Stem Cell Rev. 2005;1(2):131-8
references.pmid: 17142847
references.citation: Development. 2011 Nov;138(21):4699-708
references.pmid: 21989914
references.citation: Dev Biol. 2005 Jan 15;277(2):271-86
references.pmid: 15617674
references.citation: Development. 2008 Sep;135(17):2949-57
references.pmid: 18653557
references.citation: Development. 1993 Dec;119(4):1005-17
references.pmid: 8306871
references.citation: Lancet. 2007 Jun 23;369(9579):2106-20
references.pmid: 17586306
references.citation: Development. 1993 Mar;117(3):873-83
references.pmid: 8325243
references.citation: Brain Dev. 2009 Aug;31(7):553-7
references.pmid: 19464833
references.citation: Dev Biol. 1978 Aug;65(2):322-41
references.pmid: 680364
references.citation: Annu Rev Neurosci. 2005;28:191-222
references.pmid: 16022594
references.citation: Neuron. 2003 Apr 10;38(1):17-31
references.pmid: 12691661
references.citation: Chromosoma. 1997 Nov;106(6):348-60
references.pmid: 9362543
references.citation: Cereb Cortex. 2005 Sep;15(9):1343-55
references.pmid: 15647527
references.citation: Dev Biol. 1998 Oct 1;202(1):67-84
references.pmid: 9758704
references.citation: Dev Biol. 2008 Jul 15;319(2):179-91
references.pmid: 18501887
references.citation: J Neurosci. 2010 Nov 10;30(45):15228-40
references.pmid: 21068328
references.citation: J Cell Physiol. 2000 Mar;182(3):311-22
references.pmid: 10653597
references.citation: Development. 2010 Mar;137(5):775-84
references.pmid: 20147379
references.citation: Mol Cell Neurosci. 2002 Apr;19(4):528-38
references.pmid: 11988020
references.citation: Mol Cell Neurosci. 2008 Jan;37(1):20-31
references.pmid: 17920293
references.citation: J Neurosci. 1999 Dec 1;19(23):10357-71
references.pmid: 10575033
references.citation: J Neurosci. 2011 Feb 16;31(7):2371-81
references.pmid: 21325504
references.citation: Brain Res Rev. 2010 Sep 24;64(2):304-27
references.pmid: 20441777
references.citation: Auton Neurosci. 2009 Nov 17;151(1):3-9
references.pmid: 19783486
references.citation: Mol Cell Neurosci. 2004 Jan;25(1):30-41
references.pmid: 14962738