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???displayArticle.abstract??? Dlx3 is a homeodomain transcription factor in vertebrates, related to Distal-less in Drosophila, that is expressed in differentiating epidermal cells, in neural crest, hair follicles, dental epithelium and mesenchyme, the otic and olfactory placodes, limb bud, placenta, and in the cement gland, which is located in the extreme anterior neural plate in Xenopus embryos. This factor behaves as a transcriptional activator, and positively regulates gene expression in the skin, and negatively regulates central nervous system markers in Xenopus epidermis and anterior neural plate. A mutation in the DLX3 gene is associated with a hereditary syndrome in humans, and loss of Dlx3 function is a developmental lethal in gene-targeted mice, where it is essential for proper modeling of the labyrinthine layer of the placenta. In this review, we discuss the evolution, expression, regulation, and function of Dlx3 in mouse, amphibians, and zebrafish. Published 2000 Wiley-Liss, Inc.
Figure 3. Expression of XenopusDlx3 and Msx1 at late gastrula. In situ hybridization was performed by using stage 12, whole fixed albino embryos. Anterior view, with dorsal side on top and ventral side on the bottom. Dlx3 expression extends more dorsally than does Msx1 expression. Note: BMP activity levels are higher in the ventralectoderm than in the dorsal ectoderm, because anti-BMP antagonists (chordin, noggin, and follistatin) are secreted from the dorsal mesoderm. From Feledy et al., 1999b, with permission of Academic Press.
Figure 4. Expression of neural plate genes in animal caps injected with RNAs encoding tBR (truncated BMP receptor), Dlx3 and Msx1. Embryos were injected with the following RNAs: 2 ng of tBR, 2 ng tBR + 120 pg Dlx3, 2 ng tBR + 120 pg Msx1, or 2 ng tBR + 120 pg Dlx3 + 120 pg Msx. Animal caps (ectodermal explants) were isolated at stage 7-8 and cultured until sibling whole embryos reached stage 18 (W18; late neurula). Total RNA was isolated and analyzed for gene expression by Northern blot. Animal caps from uninjected embryos served as controls (UI). tBR repressed expression of the epidermal gene XK81(Jonas et al., 1985) and induced expression of Xag1, a cement gland marker gene (Sive et al., 1989), and Zic3, a pan-neural gene expressed in the future central nervous system region of the neural plate (Nakata et al., 1997), in the ectodermal explant tissue. Dlx3 did not inhibit expression of Xag1, but did inhibit expression of Zic3. Msx1 inhibited expression both Xag1 and Zic3. See text for discussion of these results. The epidermal keratin gene was strongly expressed in uninjected animal caps; however, neither Dlx3 nor Msx1, nor a combination of both factors increased XK81 expression significantly. Absence of signal with Xbra (Smith et al., 1991) verified the animal caps were not contaminated with mesoderm. At the bottom is a photograph of the ethidium bromide staining of the 18S region from a typical gel. Adapted from Feledy et al., 1999b, with permission of Academic Press.
Figure 5. β-Catenin repression of Dlx3 transcription in the early Xenopus embryo is not dependent on siamois function. Embryos were injected with 3 ng of β-catenin (Funayama et al., 1995) alone or in combination with 100 pg of Siamois-engrailed (Siam-enR) RNA, which encodes a dominant negative form of the siamois polypeptide (Fan and Sokol, 1997). Animal caps (ectodermal explants) were isolated at stage 7-8 and cultured until whole sibling embryos reached stage 11.5. Total RNA was isolated and analyzed for gene expression by Northern blot. Animal caps from uninjected embryos served as controls (UI). β-catenin induced expression of siamois, Xnr3, noggin, and Zic3 and inhibited expression of BMP-4 (Sasai et al., 1994) and Dlx3. Siam-enR prevents the β-catenin induction of Xnr3, noggin, and Zic3, but does not affect the repression of BMP-4 or Dlx3. At the bottom is a photograph of the ethidium bromide staining of the 18S region from a typical gel. Reprinted from Beanan et al., 2000, with permission from Elsevier Science.
