Overexpression of a slit homologue impairs convergent extension of the mesoderm and causes cyclopia in embryonic zebrafish

Yeo, S.Y., Little, M.H., Yamada, T., Miyashita, T., Halloran, M.C., Kuwada, J.Y., Huh, T.L., and Okamoto, H.
Developmental Biology   230(1): 1-17 (Journal)
Registered Authors
Halloran, Mary, Huh, Tae-Lin, Kuwada, John, Miyashita, Toshio, Okamoto, Hitoshi, Yeo, Sang-Yeob
zebrafish; Slit; cyclopia; floor plate; mesoderm; convergent extension
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Body Patterning/genetics
  • Cell Movement/genetics
  • Cloning, Molecular
  • DNA Primers/genetics
  • Eye Abnormalities/embryology
  • Eye Abnormalities/genetics
  • Gastrula/cytology
  • Gastrula/metabolism
  • Gene Expression
  • Glycoproteins*
  • Intercellular Signaling Peptides and Proteins
  • Mesoderm/cytology
  • Mesoderm/metabolism
  • Nerve Tissue Proteins/genetics*
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
11161558 Full text @ Dev. Biol.
Slit is expressed in the midline of the central nervous system both in vertebrates and invertebrates. In Drosophila, it is the midline repellent acting as a ligand for the Roundabout (Robo) protein, the repulsive receptor which is expressed on the growth cones of the commissural neurons. We have isolated cDNA fragments of the zebrafish slit2 and slit3 homologues and found that both genes start to be expressed by the midgastrula stage well before the axonogenesis begins in the nervous system, both in the axial mesoderm, and slit2 in the anterior margin of the neural plate and slit3 in the polster at the anterior end of the prechordal mesoderm. Later, expression of slit2 mRNA is detected mainly in midline structures such as the floor plate cells and the hypochord, and in the anterior margins of the neural plates in the zebrafish embryo, while slit3 expression is observed in the anterior margin of the prechordal plate, the floorplate cells in the hindbrain, and the motor neurons both in the hindbrain and the spinal cord. To study the role of Slit in early embryos, we overexpressed Slit2 in the whole embryos either by injection of its mRNA into one-cell stage embryos or by heat-shock treatment of the transgenic embryos which carries the slit2 gene under control of the heat-shock promoter. Overexpression of Slit2 in such ways impaired the convergent extension movement of the mesoderm and the rostral migration of the cells in the dorsal diencephalon and resulted in cyclopia. Our results shed light on a novel aspect of Slit function as a regulatory factor of mesodermal cell movement during gastrulation.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes