title: Synaptic protein and pan-neuronal gene expression and their regulation by Dicer-dependent mechanisms differ between neurons and neuroendocrine cells.
abstract: BACKGROUND
  Neurons in sympathetic ganglia and neuroendocrine cells in the adrenal medulla share not only their embryonic origin from sympathoadrenal precursors in the neural crest but also a range of functional features. These include the capacity for noradrenaline biosynthesis, vesicular storage and regulated release. Yet the regulation of neuronal properties in early neuroendocrine differentiation is a matter of debate and the developmental expression of the vesicle fusion machinery, which includes components found in both neurons and neuroendocrine cells, is not resolved.
  
  
  RESULTS
  Analysis of synaptic protein and pan-neuronal marker mRNA expression during mouse development uncovers profound differences between sympathetic neurons and adrenal chromaffin cells, which result in qualitatively similar but quantitatively divergent transcript profiles. In sympathetic neurons embryonic upregulation of synaptic protein mRNA follows early and persistent induction of pan-neuronal marker transcripts. In adrenal chromaffin cells pan-neuronal marker expression occurs only transiently and synaptic protein messages remain at distinctly low levels throughout embryogenesis. Embryonic induction of synaptotagmin I (Syt1) in sympathetic ganglia and postnatal upregulation of synaptotagmin VII (Syt7) in adrenal medulla results in a cell type-specific difference in isoform prevalence. Dicer 1 inactivation in catecholaminergic cells reduces high neuronal synaptic protein mRNA levels but not their neuroendocrine low level expression. Pan-neuronal marker mRNAs are induced in chromaffin cells to yield a more neuron-like transcript pattern, while ultrastructure is not altered.
  
  
  CONCLUSIONS
  Our study demonstrates that remarkably different gene regulatory programs govern the expression of synaptic proteins in the neuronal and neuroendocrine branch of the sympathoadrenal system. They result in overlapping but quantitatively divergent transcript profiles. Dicer 1-dependent regulation is required to establish high neuronal mRNA levels for synaptic proteins and to maintain repression of neurofilament messages in neuroendocrine cells.
authors: Max Planck Institute for Brain Research, Deutschordenstrasse 46 D-60528, Frankfurt, Germany. uwe.ernsberger@brain.mpg.de.
authors: Jutta
authors: J
authors: Stubbusch
authors: Priyanka
authors: P
authors: Narasimhan
authors: Katrin
authors: K
authors: Huber
authors: Klaus
authors: K
authors: Unsicker
authors: Hermann
authors: H
authors: Rohrer
authors: Uwe
authors: U
authors: Ernsberger
mesh_terms: D000818:Animals; D019439:Chromaffin Cells / Q000378:metabolism / Q000648:ultrastructure; D002838:Chromaffin System / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008817:Mice, Mutant Strains; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050857:Synaptotagmins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D020826:rab3A GTP-Binding Protein / Q000378:metabolism
chemical_list: D016900:Neurofilament Proteins; D012333:RNA, Messenger; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; C061195:neurofilament protein M; D050857:Synaptotagmins; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D020826:rab3A GTP-Binding Protein
references: Cell Tissue Res. 2012 Apr;348(1):1-27
references: 22437873
references: Mol Cell Neurosci. 2000 Jun;15(6):561-72
references: 10860582
references: J Neurosci. 2004 Jan 21;24(3):743-51
references: 14736860
references: Annu Rev Neurosci. 1993;16:129-58
references: 8460888
references: Cell. 2003 Jul 11;114(1):75-86
references: 12859899
references: Neural Dev. 2013 Jun 18;8:12
references: 23777568
references: Nature. 2011 Jul 13;476(7359):228-31
references: 21753754
references: Cell. 1990 Sep 21;62(6):1035-8
references: 2205395
references: Development. 2007 May;134(9):1663-70
references: 17376811
references: Development. 1999 Jul;126(13):2935-44
references: 10357937
references: Z Zellforsch Mikrosk Anat. 1973 Dec 6;145(3):389-416
references: 4772595
references: Mech Dev. 1997 Nov;68(1-2):115-26
references: 9431809
references: Ann Anat. 1997 Dec;179(6):495-500
references: 9442255
references: Cell. 1994 Nov 18;79(4):717-27
references: 7954835
references: Cell. 2004 Jul 23;118(2):243-55
references: 15260993
references: Handb Exp Pharmacol. 2008;(184):107-27
references: 18064413
references: Nat Med. 2007 May;13(5):604-12
references: 17417650
references: Eur J Neurosci. 2011 Nov;34(10):1563-73
references: 22103414
references: Cold Spring Harb Symp Quant Biol. 2006;71:181-8
references: 17381295
references: Development. 2006 Jan;133(1):141-50
references: 16319110
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11680-5
references: 11562488
references: J Auton Nerv Syst. 1996 Dec 14;61(3):301-12
references: 8988489
references: Curr Opin Cell Biol. 2010 Aug;22(4):496-505
references: 20561775
references: Neuron. 1999 Dec;24(4):861-70
references: 10624949
references: Eur J Biochem. 2000 Dec;267(24):6976-81
references: 11106406
references: Development. 2010 Dec;137(24):4211-20
references: 21068058
references: Prog Mol Biol Transl Sci. 2011;102:47-100
references: 21846569
references: J Neurosci. 1996 Oct 1;16(19):6208-18
references: 8815902
references: Nat Neurosci. 2002 Jan;5(1):19-26
references: 11753414
references: Traffic. 2010 Nov;11(11):1415-28
references: 20716109
references: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10898-903
references: 16040801
references: Anat Embryol (Berl). 1981;162(3):353-62
references: 7270906
references: Dev Biol. 2010 Apr 15;340(2):459-67
references: 20144605
references: Dev Biol. 2006 Oct 15;298(2):335-43
references: 16928368
references: Genome Biol. 2009;10(7):R72
references: 19570198
references: J Neurosci. 2010 Aug 11;30(32):10833-43
references: 20702712
references: Dev Biol. 2005 Mar 15;279(2):501-8
references: 15733675
references: Cell. 1996 May 3;85(3):331-43
references: 8616889
references: Dev Biol. 1999 Jun 15;210(2):411-27
references: 10357900
references: Cell Stem Cell. 2011 Dec 2;9(6):517-25
references: 22136927
references: Neural Dev. 2010 Oct 01;5:25
references: 20920300
references: J Mol Cell Biol. 2010 Jun;2(3):152-63
references: 20457670
references: Mech Dev. 2001 Oct;108(1-2):149-59
references: 11578868
references: Dev Biol. 2005 Jan 15;277(2):271-86
references: 15617674
references: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3986-91
references: 18308933
references: J Comp Neurol. 2000 Jun 12;421(4):533-42
references: 10842212
references: Nature. 2008 Apr 10;452(7188):759-63
references: 18401410
references: Neuroscience. 1999 Jan;88(2):425-35
references: 10197764
references: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3998-4003
references: 18308932
references: Cell Tissue Res. 1999 Nov;298(2):185-206
references: 10550645
references: Mech Dev. 2013 Jun-Aug;130(6-8):324-9
references: 23220335
references: Development. 1996 Jul;122(7):2079-88
references: 8681789
references: Cell. 1985 Sep;42(2):649-62
references: 3839717
references: Cell Tissue Res. 2006 Nov;326(2):205-20
references: 16786367
references: Development. 2002 Oct;129(20):4729-38
references: 12361965
references: Nat Rev Neurosci. 2010 May;11(5):329-38
references: 20354535
references: J Neurosci. 1995 Jul;15(7 Pt 1):4906-17
references: 7623121
references: Nature. 1999 May 27;399(6734):366-70
references: 10360575
references: Cell Tissue Res. 2005 Jan;319(1):1-13
references: 15565470
references: Development. 1999 Sep;126(18):4087-94
references: 10457017
references: Development. 2005 Oct;132(20):4611-9
references: 16176945