Manipulating heat shock factor-1 in Xenopus tadpoles: neuronal tissues are refractory to exogenous expression.
BACKGROUND
The aging related decline of heat shock factor-1 (HSF1) signaling may be causally related to protein aggregation diseases. To model such disease, we tried to cripple HSF1 signaling in the Xenopus tadpole.


RESULTS
Over-expression of heat shock factor binding protein-1 did not inhibit the heat shock response in Xenopus. RNAi against HSF1 mRNA inhibited the heat shock response by 70% in Xenopus A6 cells, but failed in transgenic tadpoles. Expression of XHSF380, a dominant-negative HSF1 mutant, was embryonic lethal, which could be circumvented by delaying expression via a tetracycline inducible promoter. HSF1 signaling is thus essential for embryonic Xenopus development. Surprisingly, transgenic expression of the XHSF380 or of full length HSF1, whether driven by a ubiquitous or a neural specific promoter, was not detectable in the larval brain.


CONCLUSIONS
Our finding that the majority of neurons, which have little endogenous HSF1, refused to accept transgene-driven expression of HSF1 or its mutant suggests that HSF1 levels are strictly controlled in neuronal tissue.
Dirks
Ron P
RP
Department of Biomolecular Chemistry, Radboud University Nijmegen, Nijmegen, The Netherlands.
van Geel
Remon
R
Hensen
Sanne M M
SM
van Genesen
Siebe T
ST
Lubsen
Nicolette H
NH
D000818:Animals; D001923:Brain Chemistry; D047108:Embryonic Development / Q000235:genetics; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics*; D007814:Larva; D009474:Neurons / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D014981:Xenopus
D006360:Heat-Shock Proteins; D014157:Transcription Factors
Nat Biotechnol. 2004 May;22(5):589-94
15064769
Comp Biochem Physiol A Mol Integr Physiol. 2007 Jan;146(1):131-40
17134927
Development. 1996 Oct;122(10):3173-83
8898230
J Biol Chem. 1997 May 30;272(22):14147-51
9162043
Genes Dev. 1998 Jul 1;12(13):1962-74
9649501
Biol Reprod. 2004 Jan;70(1):18-24
12954729
J Biol Chem. 2006 Feb 24;281(8):4931-7
16306048
Science. 2008 Feb 15;319(5865):916-9
18276881
J Cell Biochem. 2002;86(2):376-93
12112007
Comp Biochem Physiol A Mol Integr Physiol. 2007 May;147(1):112-21
17267255
Nature. 2000 Oct 12;407(6805):693-4
11048707
Exp Gerontol. 2005 Dec;40(12):948-58
16168601
Cell Res. 2006 Jan;16(1):99-105
16467881
Int J Hyperthermia. 2005 Aug;21(5):433-44
16048840
Neuroscience. 2004;126(3):657-63
15183515
J Biol Chem. 2005 Oct 14;280(41):34908-16
16051598
Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4839-42
15047886
Methods. 2005 Feb;35(2):199-207
15649847
Genes Dev. 1994 Jun 15;8(12):1434-47
7926743
J Biol Chem. 2004 Sep 10;279(37):38701-9
15226319
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5750-5
10811890
Cell Stress Chaperones. 2004 Summer;9(2):122-33
15497499
Dev Dyn. 2002 Dec;225(4):384-91
12454917
Gene. 1994 Sep 30;147(2):223-6
7926804
Genesis. 2001 Jul;30(3):195-7
11477707
EMBO J. 2000 Apr 3;19(7):1545-54
10747023
EMBO J. 2002 Oct 1;21(19):5164-72
12356732
FEBS Lett. 2009 Aug 20;583(16):2647-53
19393652
Nucleic Acids Res. 2000 Feb 15;28(4):E12
10648800
J Biol Chem. 2003 Dec 12;278(50):49743-50
14523008
J Biol Chem. 2005 Sep 30;280(39):33097-100
16076838
J Biol Chem. 2002 Jan 4;277(1):735-45
11679589
EMBO J. 1999 Nov 1;18(21):5943-52
10545106