FoxO genes are dispensable during gastrulation but required for late embryogenesis in Xenopus laevis.
Forkhead box (Fox) transcription factors of subclass O are involved in cell survival, proliferation, apoptosis, cell metabolism and prevention of oxidative stress. FoxO genes are highly conserved throughout evolution and their functions were analyzed in several vertebrate and invertebrate organisms. We here report on the identification of FoxO4 and FoxO6 genes in Xenopus laevis and analyze their expression patterns in comparison with the previously described FoxO1 and FoxO3 genes. We demonstrate significant differences in their temporal and spatial expression during embryogenesis and in their relative expression within adult tissues. Overexpression of FoxO1, FoxO4 or FoxO6 results in severe gastrulation defects, while overexpression of FoxO3 reveals this defect only in a constitutively active form containing mutations of Akt-1 target sites. Injections of FoxO antisense morpholino oligonucleotides (MO) did not influence gastrulation, but, later onwards, the embryos showed a delay of development, severe body axis reduction and, finally, a high rate of lethality. Injection of FoxO4MO leads to specific defects in eye formation, neural crest migration and heart development, the latter being accompanied by loss of myocardin expression. Our observations suggest that FoxO genes in X. laevis are dispensable until blastopore closure but are required for tissue differentiation and organogenesis.
Schuff
Maximilian
M
Institute of Biochemistry, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Siegel
Doreen
D
Bardine
Nabila
N
Oswald
Franz
F
Donow
Cornelia
C
Knöchel
Walter
W
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003001:Cloning, Molecular; D019465:Craniofacial Abnormalities / Q000473:pathology; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects / Q000201:enzymology; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics*; D005124:Eye Abnormalities / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D054262:Gastrulation / Q000187:drug effects / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006330:Heart Defects, Congenital / Q000473:pathology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics*
D051858:Forkhead Transcription Factors; D016376:Oligonucleotides, Antisense; D029867:Xenopus Proteins; D051057:Proto-Oncogene Proteins c-akt