An early requirement for maternal FoxH1 during zebrafish gastrulation.
The Forkhead Box H1 (FoxH1) protein is a co-transcription factor recruited by phosphorylated Smad2 downstream of several TGFbetas, including Nodal-related proteins. We have reassessed the function of zebrafish FoxH1 using antisense morpholino oligonucleotides (MOs). MOs targeting translation of foxH1 disrupt embryonic epiboly movements during gastrulation and cause death on the first day of development. The FoxH1 morphant phenotype is much more severe than that of zebrafish carrying foxh1/schmalspur (sur) DNA-binding domain mutations, FoxH1 splice-blocking morphants or other Nodal pathway mutants, and it cannot be altered by concomitant perturbations in Nodal signaling. Apart from disrupting epiboly, FoxH1 MO treatment disrupts convergence and internalization movements. Late gastrula-stage FoxH1 morphants exhibit delayed mesoderm and endoderm marker gene expression and failed patterning of the central nervous system. Probing FoxH1 morphant RNA by microarray, we identified a cohort of five keratin genes--cyt1, cyt2, krt4, krt8 and krt18--that are normally transcribed in the embryo's enveloping layer (EVL) and which have significantly reduced expression in FoxH1-depleted embryos. Simultaneously disrupting these keratins with a mixture of MOs reproduces the FoxH1 morphant phenotype. Our studies thus point to an essential role for maternal FoxH1 and downstream keratins during gastrulation that is epistatic to Nodal signaling.
Pei
Wuhong
W
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Building 35, Room 1B 205, Bethesda, MD 20892, USA.
Noushmehr
Houtan
H
Costa
Justin
J
Ouspenskaia
Maia V
MV
Elkahloun
Abdel G
AG
Feldman
Benjamin
B
D000818:Animals; D004625:Embryo, Nonmammalian / Q000502:physiology; D004627:Embryonic Induction; D051858:Forkhead Transcription Factors / Q000502:physiology*; D054262:Gastrulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D007633:Keratins / Q000235:genetics*; D055457:Nodal Protein; D016376:Oligonucleotides, Antisense; D015398:Signal Transduction; D051899:Smad2 Protein / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000502:physiology*
D051858:Forkhead Transcription Factors; D055457:Nodal Protein; D016376:Oligonucleotides, Antisense; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; C491116:foxh1 protein, zebrafish; C497786:smad2 protein, zebrafish; D007633:Keratins
Cell. 1999 Apr 2;97(1):121-32
10199408
Mol Cell Biol. 1997 Feb;17(2):529-36
9001205
BMC Genomics. 2004 Nov 8;5:87
15533245
Dev Dyn. 2005 Jan;232(1):85-97
15543604
Development. 2005 Mar;132(5):1105-16
15689372
Curr Biol. 2005 Mar 29;15(6):R213-28
15797016
Biochem Biophys Res Commun. 2005 Aug 12;333(4):1361-9
15982639
J Biol Chem. 2005 Oct 28;280(43):36355-63
16120611
Neuroendocrinology. 2005;82(3-4):208-14
16601360
Development. 2006 Jul;133(14):2757-70
16775002
Development. 1999 Dec;126(24):5621-34
10572039
Dev Dyn. 2000 Jan;217(1):109-19
10679934
Genes Dev. 2000 Feb 15;14(4):435-51
10691736
Development. 2000 Jun;127(11):2503-14
10804190
Development. 2000 Aug;127(16):3567-79
10903181
Development. 1996 Dec;123:461
9007263
C R Acad Sci III. 1997 Sep;320(9):689-700
9377174
Development. 1997 Nov;124(21):4373-82
9334285
Development. 1998 Sep;125(17):3389-97
9693142
Nature. 1998 Sep 10;395(6698):181-5
9744277
Genes Dev. 1999 Feb 1;13(3):259-69
9990851
Curr Biol. 2000 Sep 7;10(17):1041-9
10996071
Curr Biol. 2000 Sep 7;10(17):1051-4
10996072
Nat Genet. 2000 Oct;26(2):216-20
11017081
Genes Dev. 2001 May 15;15(10):1242-56
11358868
Genes Dev. 2001 May 15;15(10):1257-71
11358869
Genesis. 2001 Jul;30(3):89-93
11477681
Development. 2001 Jun;128(12):2407-20
11493559
Dev Cell. 2001 Nov;1(5):605-17
11709181
EMBO J. 2002 Jan 15;21(1-2):145-56
11782434
J Histochem Cytochem. 2002 Apr;50(4):541-8
11897807
Development. 2002 Jun;129(12):2823-34
12050132
Development. 2002 Jul;129(14):3455-68
12091315
Science. 2002 Sep 13;297(5588):1873-7
12228718
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12651-6
12271129
Dev Biol. 2002 Oct 15;250(2):263-79
12376102
Dev Dyn. 2002 Dec;225(4):448-56
12454922
Cell. 2002 Nov 27;111(5):647-59
12464177
Cell. 2003 Jun 13;113(6):685-700
12809600
Development. 2003 Dec;130(23):5589-99
14522874
Genome Res. 2003 Dec;13(12):2700-7
14613981
Development. 2004 Oct;131(20):5065-78
15459100
Genes Dev. 1993 Jul;7(7B):1436-46
7687227
Development. 1993 Apr;117(4):1261-74
8104775
Development. 1993 Dec;119(4):1107-18
8306877
Development. 1994 Apr;120(4):843-52
7600961
EMBO J. 1995 Dec 1;14(23):5965-73
8846789
Dev Dyn. 1995 Jul;203(3):253-310
8589427
Nature. 1996 Oct 24;383(6602):691-6
8878477
Int J Dev Biol. 1996 Oct;40(5):929-40
8946241
Mech Dev. 1998 Dec;79(1-2):17-27
10349617