Dorsoventral Patterning of the Zebrafish Embryo
85
fates. Recent evidence indicates that Bmp4 can function as an instructive morphogen which determines positional identities along the entire
dorsoventral axis in a dose-dependent fashion (Dosch et al. 1997), while
Chordin, Noggin, and Follistatin attenuate this ventralizing activity on
the dorsal side of the embryo by physical interaction with, and inhibition of, Bmp proteins (Fainsod et al. 1997; Piccolo et al. 1996; Zimmerman and Harland 1996), thereby leading to the establishment of the
putative dorsoventral gradient of Bmp4 activity. According to this
model, the specification of dorsal-most fates occurs in a kind of default
pathway, when Bmp activity is entirely abolished, while intermediate
Bmp levels lead to the establishment of intermediate fates like muscle,
and highest Bmp levels to the establishment of ventral-most fates such
as blood.
Final evidence, however, that early dorsoventral patterning does
indeed occur according to this model, as well as the identification of the
involved genes, requires genetical analyses via mutant embryos in
which the activity of the respective genes is reduced (hypomorphic
mutations) or entirely lost (amorphic mutations).
6.3 The Genetics of the Fish
Hypomorphic and amorphic mutants have been isolated in the zebrafish. Here, large-scale screens for mutants with defects in various
developmental processes have been carried out. After random introduction of point mutations via the chemical ethylnitrosourea (ENU) and
classic inbreeding steps, homozygous mutant embryos were generated
(Haffter et al. 1996; Mullins et al. 1994). Thereby, thousands of zygotic
recessive mutations were isolated and assigned to several hundred complementation groups; among them at least six complementation groups
defining six genes zygotically required for ventral development and two
complementation groups defining two genes zygotically required for
dorsal development (Hammerschmidt et al. 1996a; Mullins et al. 1996;
Solnica-Krezel et al. 1996). At this point of their identification, these
genes are defined only by the phenotype they cause in the embryo upon
mutation. Their molecular nature, however, is not known a priori, and
has to be determined in further steps.
85
fates. Recent evidence indicates that Bmp4 can function as an instructive morphogen which determines positional identities along the entire
dorsoventral axis in a dose-dependent fashion (Dosch et al. 1997), while
Chordin, Noggin, and Follistatin attenuate this ventralizing activity on
the dorsal side of the embryo by physical interaction with, and inhibition of, Bmp proteins (Fainsod et al. 1997; Piccolo et al. 1996; Zimmerman and Harland 1996), thereby leading to the establishment of the
putative dorsoventral gradient of Bmp4 activity. According to this
model, the specification of dorsal-most fates occurs in a kind of default
pathway, when Bmp activity is entirely abolished, while intermediate
Bmp levels lead to the establishment of intermediate fates like muscle,
and highest Bmp levels to the establishment of ventral-most fates such
as blood.
Final evidence, however, that early dorsoventral patterning does
indeed occur according to this model, as well as the identification of the
involved genes, requires genetical analyses via mutant embryos in
which the activity of the respective genes is reduced (hypomorphic
mutations) or entirely lost (amorphic mutations).
6.3 The Genetics of the Fish
Hypomorphic and amorphic mutants have been isolated in the zebrafish. Here, large-scale screens for mutants with defects in various
developmental processes have been carried out. After random introduction of point mutations via the chemical ethylnitrosourea (ENU) and
classic inbreeding steps, homozygous mutant embryos were generated
(Haffter et al. 1996; Mullins et al. 1994). Thereby, thousands of zygotic
recessive mutations were isolated and assigned to several hundred complementation groups; among them at least six complementation groups
defining six genes zygotically required for ventral development and two
complementation groups defining two genes zygotically required for
dorsal development (Hammerschmidt et al. 1996a; Mullins et al. 1996;
Solnica-Krezel et al. 1996). At this point of their identification, these
genes are defined only by the phenotype they cause in the embryo upon
mutation. Their molecular nature, however, is not known a priori, and
has to be determined in further steps.