The roles of Groucho/Tle in left-right asymmetry and Kupffer's vesicle organogenesis.
The heart is the first organ to form and function in the vertebrate embryo. Furthermore, differences between the left and right sides of the embryo become first detectable during cardiac development. We observed strong cardiac laterality phenotypes in medaka embryos by manipulating Groucho protein activity. The phenotypes produced by misexpressing Tle4 and the dominant-negative Aes reveal a general effect of these corepressor proteins on left-right (LR) development. With the help of an inducible expression system, we were able to define temporally different phases for these effects. In an early phase during gastrulation, Groucho proteins regulate Brachyury expression in the dorsal forerunner cells, which later gives rise to the Kupffer's vesicle (KV). The interference of endogenous Groucho proteins by misexpression of Aes leads to KVs of reduced size, whereas overexpression of Tle4 results in enlarged KVs. The expression level of the cilia marker Lrd was also affected both positively and negatively from these treatments. In the late phase during somitogenesis, Groucho proteins regulate the asymmetric activities of Nodal and Lefty genes. Altering canonical Wnt signaling produced similar results in late embryos, however, this did not affect KV morphogenesis or Lrd expression in early embryos. Therefore, changes in Kupffer's vesicle morphogenesis and the laterality of visceral organs following alterations in Groucho corepressor levels demonstrate two distinct phases in which Groucho proteins help establish LR asymmetry in medaka fish.
Bajoghli
Baubak
B
Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Veterinärplatz 1, A-1210 Vienna, Austria.
Aghaallaei
Narges
N
Soroldoni
Daniele
D
Czerny
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology; D005326:Fetal Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D055458:Left-Right Determination Factors; D008969:Molecular Sequence Data; D038081:Organogenesis / Q000502:physiology*; D009990:Oryzias / Q000196:embryology*; D010802:Phylogeny; D012097:Repressor Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D020825:T-Box Domain Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000098908:Brachyury Protein
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D055458:Left-Right Determination Factors; D012097:Repressor Proteins; D020825:T-Box Domain Proteins; D016212:Transforming Growth Factor beta; D000098908:Brachyury Protein