Embryonic Patterning of Xenopus Mesoderm by Bmp-4
175
have a passive role in signalling, because positional information read by
cells in the marginal zone corresponds to the local BMP-4 activity,
which becomes graded by organizer signals. Put differently, what appears macroscopically to be induction (dorsalization), is microscopically modification of ventral morphogen read-out.
While we have focused here on Bmp-4, there are at least four other
TGF-13 type BMPs expressed in early Xenopus embryos: Bmp-2 (Nishimatsu et al. 1992; Clement et al. 1995; Hemmati-Brivanlou and Thomsen 1995), two Bmp-7 related genes (Hawley et al. 1995; Wang et al.
1997), and anti-dorsalizing morphogenetic protein (ADMP) (Moos et
al. 1995), all of which are ventralizing. While maternally expressed
Bmp-2 may be involved in mesoderm induction, the low levels of
protein present at gastrulation and the fact that antisense injection of
Bmp-2 mRNA does not show neuralizing effects [in contrast to antisense Bmp-4 mRNA; (Sasai et al. 1995)], makes a function during
gastrulation less likely. Bmp-7 is expressed in the marginal zone during
gastrula stages and shows activities similar to Bmp-4, suggesting that it
may act in concert with Bmp-4. In addition, it can form functional
heterodimers with Bmp-4 (Nishimatsu and Thomsen 1998). ADMP is,
curiously, expressed in the organizer and may be important to fine-tune
coexpressed BMP antagonists (Moos et al. 1995).
Disruption of the mouse Bmp-4 gene is embryonically lethal, with
embryos dying around gastrulation, but penetrance is variable (Winnier
et al. 1995). In contrast, Bmp-7 (Dudley et al. 1995) and Bmp-2 (Zhang
and Bradley 1996) mouse mutants do not show defects in d/v patterning.
This suggests that in mice, various BMPs act redundantly during gastruFig. 3. Model of mesodermal patterning at the gastrula stage by a Bmp-4 morphogen gradient. Bmp-4 mRNA is uniformly expressed in the marginal zone
except in the dorsal domain (fine dashed line). Noggin (continuous line) is expressed in the dorsal domain. Their protein products overlap dorsolaterally
leading to attenuated BMP-4 activity (coarse dashed line), resulting in dorsal
(future notochord), dorsolateral (future muscle), and lateroventral (future
blood, lateral plate mesenchyme) positional values. Xvent-l has a high dose requirement for BMP-4. myf5 has a requirement for a low ,and is inhibited by a
high, BMP-4 dose. Xvent-2 has a requirement for a low BMP-4 dose. The
black and white gradient in the lower panel indicates the BMP-4 activity gradient in the gastrula marginal zone which regulates formation of the indicated
mesodermal tissues. (From Dosch et al. 1997)
175
have a passive role in signalling, because positional information read by
cells in the marginal zone corresponds to the local BMP-4 activity,
which becomes graded by organizer signals. Put differently, what appears macroscopically to be induction (dorsalization), is microscopically modification of ventral morphogen read-out.
While we have focused here on Bmp-4, there are at least four other
TGF-13 type BMPs expressed in early Xenopus embryos: Bmp-2 (Nishimatsu et al. 1992; Clement et al. 1995; Hemmati-Brivanlou and Thomsen 1995), two Bmp-7 related genes (Hawley et al. 1995; Wang et al.
1997), and anti-dorsalizing morphogenetic protein (ADMP) (Moos et
al. 1995), all of which are ventralizing. While maternally expressed
Bmp-2 may be involved in mesoderm induction, the low levels of
protein present at gastrulation and the fact that antisense injection of
Bmp-2 mRNA does not show neuralizing effects [in contrast to antisense Bmp-4 mRNA; (Sasai et al. 1995)], makes a function during
gastrulation less likely. Bmp-7 is expressed in the marginal zone during
gastrula stages and shows activities similar to Bmp-4, suggesting that it
may act in concert with Bmp-4. In addition, it can form functional
heterodimers with Bmp-4 (Nishimatsu and Thomsen 1998). ADMP is,
curiously, expressed in the organizer and may be important to fine-tune
coexpressed BMP antagonists (Moos et al. 1995).
Disruption of the mouse Bmp-4 gene is embryonically lethal, with
embryos dying around gastrulation, but penetrance is variable (Winnier
et al. 1995). In contrast, Bmp-7 (Dudley et al. 1995) and Bmp-2 (Zhang
and Bradley 1996) mouse mutants do not show defects in d/v patterning.
This suggests that in mice, various BMPs act redundantly during gastruFig. 3. Model of mesodermal patterning at the gastrula stage by a Bmp-4 morphogen gradient. Bmp-4 mRNA is uniformly expressed in the marginal zone
except in the dorsal domain (fine dashed line). Noggin (continuous line) is expressed in the dorsal domain. Their protein products overlap dorsolaterally
leading to attenuated BMP-4 activity (coarse dashed line), resulting in dorsal
(future notochord), dorsolateral (future muscle), and lateroventral (future
blood, lateral plate mesenchyme) positional values. Xvent-l has a high dose requirement for BMP-4. myf5 has a requirement for a low ,and is inhibited by a
high, BMP-4 dose. Xvent-2 has a requirement for a low BMP-4 dose. The
black and white gradient in the lower panel indicates the BMP-4 activity gradient in the gastrula marginal zone which regulates formation of the indicated
mesodermal tissues. (From Dosch et al. 1997)