Tao J, Kuliyev E, Wang X et al.BMP4-dependent expression of Xenopus Grainyhead-like 1 is essential for epidermal differentiation. Development 132:1021-1034

Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Development (Impact Factor: 6.46). 04/2005; 132(5):1021-34. DOI: 10.1242/dev.01641
Source: PubMed


Morphogen-dependent epidermal-specific transacting factors have not been defined in vertebrates. We demonstrate that a member of the grainyhead transcription factor family, Grainyhead-like 1 (XGrhl1) is essential for ectodermal ontogeny in Xenopus laevis. Expression of this factor is restricted to epidermal cells. Moreover, XGrhl1 is regulated by the BMP4 signaling cascade. Disruption of XGrhl1 activity in vivo results in a severe defect in terminal epidermal differentiation, with inhibition of XK81A1 epidermal keratin gene expression, a key target of BMP4 signaling. Furthermore, transcription of the XK81A1 gene is modulated directly by binding of XGRHL1 to a promoter-localized binding motif that is essential for high-level expression. These results establish a novel developmental role for XGrhl1 as a crucial tissue-specific regulator of vertebrate epidermal differentiation.

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    • "The water loss is associated with reduced expression of the gene encoding TGase1, an enzyme that promotes cross-linking of parts of the stratum corneum, thus preventing the movement of water and solutes [22]. Likewise, in Xenopus, a Grh-like gene (Xgrh1) has been implicated in the development of the epidermis [13]. One of its primary targets is epidermal keratin. "
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    ABSTRACT: The transcription factors of the LSF/Grainyhead (GRH) family are characterized by the possession of a distinctive DNA-binding domain that bears no clear relationship to other known DNA-binding domains, with the possible exception of the p53 core domain. In triploblastic animals, the LSF and GRH subfamilies have diverged extensively with respect to their biological roles, general expression patterns, and mechanism of DNA binding. For example, Grainyhead (GRH) homologs are expressed primarily in the epidermis, and they appear to play an ancient role in maintaining the epidermal barrier. By contrast, LSF homologs are more widely expressed, and they regulate general cellular functions such as cell cycle progression and survival in addition to cell-lineage specific gene expression. To illuminate the early evolution of this family and reconstruct the functional divergence of LSF and GRH, we compared homologs from 18 phylogenetically diverse taxa, including four basal animals (Nematostella vectensis, Vallicula multiformis, Trichoplax adhaerens, and Amphimedon queenslandica), a choanoflagellate (Monosiga brevicollis) and several fungi. Phylogenetic and bioinformatic analyses of these sequences indicate that (1) the LSF/GRH gene family originated prior to the animal-fungal divergence, and (2) the functional diversification of the LSF and GRH subfamilies occurred prior to the divergence between sponges and eumetazoans. Aspects of the domain architecture of LSF/GRH proteins are well conserved between fungi, choanoflagellates, and metazoans, though within the Metazoa, the LSF and GRH families are clearly distinct. We failed to identify a convincing LSF/GRH homolog in the sequenced genomes of the algae Volvox carteri and Chlamydomonas reinhardtii or the amoebozoan Dictyostelium purpureum. Interestingly, the ancestral GRH locus has become split into two separate loci in the sea anemone Nematostella, with one locus encoding a DNA binding domain and the other locus encoding the dimerization domain. In metazoans, LSF and GRH proteins play a number of roles that are essential to achieving and maintaining multicellularity. It is now clear that this protein family already existed in the unicellular ancestor of animals, choanoflagellates, and fungi. However, the diversification of distinct LSF and GRH subfamilies appears to be a metazoan invention. Given the conserved role of GRH in maintaining epithelial integrity in vertebrates, insects, and nematodes, it is noteworthy that the evolutionary origin of Grh appears roughly coincident with the evolutionary origin of the epithelium.
    Full-text · Article · Apr 2010 · BMC Evolutionary Biology
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    • "In contrast, Xema (Xenopus ectodermally expressed mesendoderm antagonist; Suri et al., 2005) is strongly activated. Furthermore, we observed a slight activation of Grhl1, a transcription factor that was shown to be essential for ectodermal ontogeny and necessary for expression of epidermal genes (Tao et al., 2005). Upregulation of epidermal cadherin and epidermal keratin, indicating epidermal differentiation, can only be observed for FoxO1 injection, suggesting functional differences between the FoxO genes. "
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    ABSTRACT: Forkhead box (Fox) transcription factors of subclass O are involved in cell survival, proliferation, apoptosis, cell metabolism and prevention of oxidative stress. FoxO genes are highly conserved throughout evolution and their functions were analyzed in several vertebrate and invertebrate organisms. We here report on the identification of FoxO4 and FoxO6 genes in Xenopus laevis and analyze their expression patterns in comparison with the previously described FoxO1 and FoxO3 genes. We demonstrate significant differences in their temporal and spatial expression during embryogenesis and in their relative expression within adult tissues. Overexpression of FoxO1, FoxO4 or FoxO6 results in severe gastrulation defects, while overexpression of FoxO3 reveals this defect only in a constitutively active form containing mutations of Akt-1 target sites. Injections of FoxO antisense morpholino oligonucleotides (MO) did not influence gastrulation, but, later onwards, the embryos showed a delay of development, severe body axis reduction and, finally, a high rate of lethality. Injection of FoxO4MO leads to specific defects in eye formation, neural crest migration and heart development, the latter being accompanied by loss of myocardin expression. Our observations suggest that FoxO genes in X. laevis are dispensable until blastopore closure but are required for tissue differentiation and organogenesis.
    Full-text · Article · Nov 2009 · Developmental Biology
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    • "This suggests that the inhibition observed is not due to direct interaction of BMP-activated phosphorylated Smads with XSip1 but probably involves indirect convergence of Smad signals and XSip1 on target gene promoters. Coinjection of CA-Alk3 RNA with XSip1 RNA affected the ability of XSip1 to repress Gata2, a marker of both superficial and deep layers of the ventral ectoderm, but did not block its ability to repress other epidermal genes, such as Epidermal keratin, Grainyhead-like-1 (Tao et al., 2005) and TA-2 that are selectively expressed in the superficial layer and Vestigial like 4 (Vgl-4) and Hyaluronan synthase 1 (Hya-1) (Chalmers et al., 2002), which are deep cell specific markers (Figs. 2E–I and data not shown). Similar results were obtained in embryos (Fig. 2J Fig. 3. Repression of the BMP4 promoter by Sip1. "
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    ABSTRACT: The DNA-binding transcription factor Smad-interacting protein-1 (Sip1) (also named Zfhx1b/ZEB2) plays essential roles in vertebrate embryogenesis. In Xenopus, XSip1 is essential at the gastrula stage for neural tissue formation, but the precise molecular mechanisms that underlie this process have not been fully identified yet. Here we show that XSip1 functions as a transcriptional repressor during neural induction. We observed that constitutive activation of BMP signaling prevents neural induction by XSip1 but not the inhibition of several epidermal genes. We provide evidence that XSip1 binds directly to the BMP4 proximal promoter and modulates its activity. Finally, by deletion and mutational analysis, we show that XSip1 possesses multiple repression domains and that CtBPs contribute to its repression activity. Consistent with this, interference with XCtBP function reduced XSip1 neuralizing activity. These results suggest that Sip1 acts in neural tissue formation through direct repression of BMP4 but that BMP-independent mechanisms are involved as well. Our data also provide the first demonstration of the importance of CtBP binding in Sip1 transcriptional activity in vivo.
    Full-text · Article · Jul 2007 · Developmental Biology
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