Dorsoventral Patterning of the Zebrafish Embryo
97
chordino expression domain. Unlike in Xenopus, expression of chordino does not remain restricted to the dorsal mesoderm, but starts to
spread into more lateral regions shortly after the onset of gastrulation.
This spreading of the chordino expression appears to occur in a kind of
progressive homogenetic induction, as it is not seen in chordino mutants, where chordino expression remains restricted to the dorsal-most
region of the embryo (Schulte-Merker et a1. 1997). This indicates that
the lateral spreading requires functional Chordino protein, and that
during normal development, Chordino acts as an inducer of its own
expression in neighboring cells. This positive autoregulation is achieved
indirectly via an inhibition of Bmp2/417, as suggested by the effects of
bmp21417 overexpression and BMP inhibition on induced chordino expression.
In summary, the ventral retraction of bmp21417 expression and the
lateral spreading of the expression of chordino appears to occur by the
following mechanism: Bmp2/417 act as positive regulators of their own
expression, as described above, and as negative regulators of chordino
expression. Chordino protein, when diffusing from its site of production, binds and inactivates BMP proteins, which has two synergistic
effects on the transcriptional level in the neighboring cells: a repression
of bmp21417 transcription and a de-repression of the transcription of
chordino.
6.10 Tolloid/Bmpl Acts as an Inhibitor of Chordino
Having learned that Chordino is a rather efficient signaling molecule
and positive auto inducer, it is tempting to imagine that the embryo has
developed means to restrict Chordino action and to protect ventral-most
regions from Chordino signaling. A candidate for such a potential
inhibitor of Chordino named Tolloid has been recently isolated in the
fruit fly Drosophila (Finelli et a1. 1994), Xenopus (Piccolo et al. 1997),
and zebrafish (Blader et al. 1997). A very similar protein had been
previously isolated in mammals, named Bone Morphogenetic protein
Bmpl. Unlike the other Bmp proteins, Bmpl is not a TGF~ molecule,
but a metalloprotease of the astacin family. It was designated as a Bone
Morphogenetic protein, because it was originally identified together
with Bmp2 and Bmp3 from demineralized bone that induced ectopic
97
chordino expression domain. Unlike in Xenopus, expression of chordino does not remain restricted to the dorsal mesoderm, but starts to
spread into more lateral regions shortly after the onset of gastrulation.
This spreading of the chordino expression appears to occur in a kind of
progressive homogenetic induction, as it is not seen in chordino mutants, where chordino expression remains restricted to the dorsal-most
region of the embryo (Schulte-Merker et a1. 1997). This indicates that
the lateral spreading requires functional Chordino protein, and that
during normal development, Chordino acts as an inducer of its own
expression in neighboring cells. This positive autoregulation is achieved
indirectly via an inhibition of Bmp2/417, as suggested by the effects of
bmp21417 overexpression and BMP inhibition on induced chordino expression.
In summary, the ventral retraction of bmp21417 expression and the
lateral spreading of the expression of chordino appears to occur by the
following mechanism: Bmp2/417 act as positive regulators of their own
expression, as described above, and as negative regulators of chordino
expression. Chordino protein, when diffusing from its site of production, binds and inactivates BMP proteins, which has two synergistic
effects on the transcriptional level in the neighboring cells: a repression
of bmp21417 transcription and a de-repression of the transcription of
chordino.
6.10 Tolloid/Bmpl Acts as an Inhibitor of Chordino
Having learned that Chordino is a rather efficient signaling molecule
and positive auto inducer, it is tempting to imagine that the embryo has
developed means to restrict Chordino action and to protect ventral-most
regions from Chordino signaling. A candidate for such a potential
inhibitor of Chordino named Tolloid has been recently isolated in the
fruit fly Drosophila (Finelli et a1. 1994), Xenopus (Piccolo et al. 1997),
and zebrafish (Blader et al. 1997). A very similar protein had been
previously isolated in mammals, named Bone Morphogenetic protein
Bmpl. Unlike the other Bmp proteins, Bmpl is not a TGF~ molecule,
but a metalloprotease of the astacin family. It was designated as a Bone
Morphogenetic protein, because it was originally identified together
with Bmp2 and Bmp3 from demineralized bone that induced ectopic