Inhibitory Patterning of the Anterior Neural Plate in Xenopus by Homeodomain Factors Dlx3 and Msx1

Feledy, Jules A.; Beanan, Maureen J.; Sandoval, John J; Goodrich, Jennifer S.; Lim, Jae Hwan; Matsuo-Takasaki, Mami; Sato, Sheryl M.; Sargent, Thomas D.

doi:10.1006/dbio.1999.9374

Cited by 112 publications

(100 citation statements)

References 46 publications

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“…40). Interestingly, Dlx3 expression patterns during Xenopus development depends in part upon BMP signaling gradients (41,42). Inhibition of these gradients using the BMP receptor antagonist chordin resulted in a dose-sensitive inhibition of Dlx3, Dlx5, and Dlx6 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Smad6 Represses Dlx3 Transcriptional Activity through Inhibition of DNA Binding

Berghorn¹,

Clark-Campbell²,

Han³

et al. 2006

Journal of Biological Chemistry

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Dlx3 (Distal-less 3) is a homeobox-containing transcription factor required for normal placental development in mice. Here we demonstrate that Dlx3 interacts with Smad6, a member of a larger family of transcriptional regulators generally thought to regulate transforming growth factor ␤/bone morphogenetic protein signaling. Immunocytochemical and immunoprecipitation studies demonstrate overlapping nuclear localization and physical interaction between Dlx3 and Smad6 in human choriocarcinoma cells and in differentiated trophoblasts from human placenta. In vitro protein interaction studies mapped the Smad6 interaction domain within Dlx3 to residues 80 -163, a region of Dlx3 that includes a portion of the homeodomain. Dlx3 and Dlx4 share homology within this region, and Dlx4 was also found to bind Smad6. Using the Esx1 gene promoter as a model for a Dlx3-responsive gene, studies demonstrate two near consensus Dlx3 binding sites within the proximal 2.3 kb of the transcription start site. Interestingly, binding of Dlx3 to one of these two sites was inhibited by interaction with Smad6. Consistent with this result, expression of an Esx1 promoter luciferase reporter was increased by overexpression of Dlx3; this effect was reversed with co-expression of Smad6. Further, small interference RNAmediated knockdown of endogenous Smad6 increased Dlx3-dependent expression of the Esx1 gene promoter. Thus, Smad6 appears to functionally interact with Dlx3, altering the ability of Dlx3 to bind target gene promoters. Smad6 appears to play a modulatory role in the regulation of Dlx3-dependent gene transcription within placental trophoblasts.

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Section: Discussionmentioning

confidence: 99%

Smad6 Represses Dlx3 Transcriptional Activity through Inhibition of DNA Binding

Berghorn¹,

Clark-Campbell²,

Han³

et al. 2006

Journal of Biological Chemistry

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“…In Xenopus, Msx1 is expressed in the area of the prospective neural crest and in the epidermal ectoderm, ventrolateral to the neural crest region (Tribulo et al, 2003), where it acts as a ventralizing factor (Ramos and Robert, 2005). Msx1 represses zic gene expression in neuralized animal caps (ectodermal explants) of Xenopus (Feledy et al, 1999;Yamamoto et al, 2000;Monsoro-Burq et al, 2005). Thus, intermediate levels of BMP induce msx1 expression and Msx1, in turn, may prevent zic gene expression in regions lateral to the neural plate.…”

Section: Regulation Of Zic Gene Expressionmentioning

confidence: 99%

“…Dlx3, also a direct target of BMP signaling (Park and Morasso, 2002), is another ventralizing transcription factor. It is important in positioning the neural plate border and has been shown to repress zic gene expression in Xenopus in a manner similar to Msx1 (Feledy et al, 1999). Thus, regulatory mechanisms are emerging that limit the expression of zic genes (Fig.…”

Section: Regulation Of Zic Gene Expressionmentioning

confidence: 99%

Emerging roles for zic genes in early development

Merzdorf

2007

Developmental Dynamics

131

126

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“…To test this hypothesis, we examined the expression levels of epidermal and neural marker genes in xEIG121L-depleted ectodermal explants. Our quantitative RT-PCR analyses showed that the expression levels of epidermal genes, Msx1 (21), Dlx3 (22), Grhl1 (23), Cv2 (17), Xlr (Xolloid-related) (11), and Szl (15), were dramatically decreased in the xEIG121L-depleted ectodermal explants, compared with those in control MO-injected ectodermal explants (Fig. 4A).…”

Section: Knockdown Of Xeig121l Causes Inhibition Of Epidermal Differementioning

confidence: 92%

“…These transcription factors induce more restricted proepidermal genes such as Dlx3/5, Grhl1, and Xap2 (8,22,23). These genes in turn regulate epidermal structural genes such as epidermal keratin.…”

mentioning

confidence: 99%

A Transmembrane Protein EIG121L Is Required for Epidermal Differentiation during Early Embryonic Development

Araki

Kusakabe

Nishida

2011

Journal of Biological Chemistry

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Epidermal differentiation in the ventral ectoderm of Xenopus embryos is regulated by the bone morphogenetic protein (BMP) pathway. However, it remains unclear how the BMP pathway is activated and induces the epidermal fate in the ventral ectoderm. Here, we identify a novel player in the BMP pathway that is required for epidermal differentiation during Xenopus early embryonic development. We show that Xenopus EIG121L (xEIG121L) protein, an evolutionarily conserved transmembrane protein, is expressed in the ventral ectoderm at the gastrula and neurula stages. Almost complete knockdown of xEIG121L protein with antisense morpholino oligonucleotides in early Xenopus embryos results in severe developmental defects, including the inhibition of epidermal differentiation and the induction of neural genes. Remarkably, our analysis shows that BMP/Smad1 signaling is severely suppressed in the xEIG121L knockdown ectoderm. Moreover, immunoprecipitation and immunostaining experiments suggest that xEIG121L protein physically interacts, and co-localizes, with BMP receptors. Thus, our results identify a novel regulator of the BMP pathway that has a positive role in BMP signaling and plays an essential role in epidermal differentiation during early embryonic development.The bone morphogenetic protein (BMP) 4 signaling pathway has key roles in embryonic development, adult homeostasis, and diseases (1-6). A secreted dimeric ligand binds to a heterotetrameric cell surface complex of two type II and two type I kinase receptors. The type II receptor phosphorylates the type I receptor and thereby activates it. The activated type I receptor phosphorylates receptor-activated Smad (Smad1, Smad5, and Smad8 in mammals) at C-terminal serines. These phosphorylated Smad proteins form heterotrimeric complexes with the common-mediator Smad (Smad4 in mammals), and these complexes accumulate in the nucleus where they participate in the transcriptional control of target genes with sequence-specific transcription factors, co-activators, and co-repressors (1-6).In Xenopus embryos, the BMP pathway determines cell fates at the gastrula stage (7,8). In the ectoderm, the ventral region, in which the BMP pathway is activated, differentiates into epidermal tissues, and the dorsal region, in which the BMP pathway is inhibited, differentiates into neural tissues. Previous studies have shown that various factors regulate the BMP pathway during early embryonic development (7, 9 -18). Secreted factors such as Chordin, Noggin, and Follistatin bind to BMPs (BMP2, BMP4, BMP7, and anti-dorsalizing morphogenetic protein) in the extracellular space and inactivate BMP signaling at the gastrula stage, thereby inducing neural differentiation in the dorsal ectoderm (9,10,12,19). In the ventral region, secreted factors Sizzled (Szl) and Crossveinless-2 (Cv2) are induced by the BMP pathway and serve as BMP feedback inhibitors (15,17). These molecules comprise a network of BMP interacting proteins to establish the dorsoventral body axis in early embryos.In epidermal differ...

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Inhibitory Patterning of the Anterior Neural Plate in Xenopus by Homeodomain Factors Dlx3 and Msx1

Cited by 112 publications

References 46 publications

Smad6 Represses Dlx3 Transcriptional Activity through Inhibition of DNA Binding

Smad6 Represses Dlx3 Transcriptional Activity through Inhibition of DNA Binding

Emerging roles for zic genes in early development

A Transmembrane Protein EIG121L Is Required for Epidermal Differentiation during Early Embryonic Development

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