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Epidermal fate in Xenopus ectoderm has been shown to be induced by a secreted growth factor, Bone Morphogenetic Protein 4 (BMP4). However, the molecular mechanism mediating this response is poorly understood. Here, we show that the expression of the homeobox gene, msx1, is an immediate early response to BMP4 in Xenopus embryos. The timing of expression and embryonic distribution of msx1 parallel those described for BMP4. Moreover, overexpression of msx1 in early Xenopus embryos leads to their ventralization as described for BMP4. Consistent with mediating a BMP type of signaling, overexpression of msx1 is sufficient to induce epidermis in dissociated ectoderm cells, which would otherwise form neural tissue. Finally, msx1 can also rescue neuralization imposed by a dominant negative BMP receptor (tBR) in ectodermal explants. We propose that Xenopus msx1 acts as a mediator of BMP signaling in epidermal induction and inhibition of neural differentiation.
Fig. 3. Spatial distribution of msx1 transcripts during early Xenopus development. Whole-mount in situ hybridization of albino embryos using a digoxigenin-labeled antisense msx1 probe. msx1 transcripts are detectable from midgastrula stages (stage 11; A,B). Dorsal (A) and lateral (B) views indicate the localization of msx1 transcripts in the ventral animal and marginal regions of the embryo. Dorsal (C) and lateral (D) views at early neurula stages indicate that the expression of msx1 gradually divides into ventral and dorsal regions, and that the dorsal expression is restricted to the border of epidermis and neural plate. a, anterior; p, posterior; d, dorsal; v, ventral. (E,F) Dorsal and ventral views of stage 17 embryos, respectively, and anterior is up. As the neural tube closes, the expression of msx1 is observed in the dorsal neural tube (E) and the heart and around blastopore on the ventral side (F). At tailbud (G) and tadpole (H) stages, expression is detected in fin, cement gland, dorsal neural tube, otic vesicle and, broadly, in the ventral region.
Fig. 5. msx1 ventralizes Xenopus embryos. msx1 RNA (1.0 or 2.0 ng) was injected into the animal pole of 2-cell embryos which were grown to tadpole stages (stage 31). The uninjected embryo is used as a control.
msx1 (msh homeobox 1) gene expression in Xenopus laevis embryo via in situ hybridization, NF stage 11, dorsal view, anterior up.
msx1 (msh homeobox 1) gene expression in Xenopus laevis embryo via in situ hybridization, NF stage 11, lateral view, anterior up, dorsal right.
msx1 (msh homeobox 1) gene expression in Xenopus laevis embryo via in situ hybridization, NF stage 13-14, dorsal view, anterior up.
msx1 (msh homeobox 1) gene expression in Xenopus laevis embryo via in situ hybridization, NF stage 13-14, lateral view, anteriorleft, dorsal up.
msx1 (msh homeobox 1) gene expression in Xenopus laevis embryo via in situ hybridization, NF stage 17, dorsal view, anterior up.
msx1 (msh homeobox 1) gene expression in Xenopus laevis embryo via in situ hybridization, NF stage 17, ventral view, anterior up.
msx1 (msh homeobox 1) gene expression in Xenopus laevis embryo via in situ hybridization, NF stage 27, lateral view, anteriorleft, dorsal up.
