Choice of either β-catenin or Groucho/TLE as a co-factor for Xtcf-3 determines dorsal-ventral cell fate of diencephalon during Xenopus development

Tsuji, Saori; Hashimoto, Chikara

doi:10.1007/s00427-005-0474-0

Cited by 12 publications

(9 citation statements)

References 83 publications

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“…A DHCR7 rescue construct was created by inserting a PCR fragment between the EcoRI and AscI sites of pCS2 AT+ (Tsuji and Hashimoto, 2005). Primers used were DHCR7wt-F (5Ј-GGAATTCCGCACCATGGGAGAGCGGAGAAGAG-3Ј) and DHCR7wt-R (5Ј-GGCGCGCCAAAGGTGAGGCGGTAAAA-CA-3Ј).…”

Section: Plasmidsmentioning

confidence: 99%

Negative regulation of Hedgehog signaling by the cholesterogenic enzyme 7-dehydrocholesterol reductase

2006

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Cholesterol regulates Hedgehog (Hh) signaling during early vertebrate development. Smith-Lemli-Opitz syndrome (SLOS) is caused by defects in 7-dehydrocholesterol reductase (DHCR7), an enzyme catalyzing the final step of cholesterol biosynthesis. Many developmental malformations attributed to SLOS occur in tissues and organs where Hh signaling is required for development, but the precise role of DHCR7 deficiency in this disease remains murky. We report that DHCR7 and Sonic Hedgehog (Shh) are coexpressed during midline development in Xenopus embryos. DHCR7 has previously been implicated to function as a positive regulator of Hh signaling that acts to regulate the cholesterol adduction of Hh ligand or to affect Hh signaling in the responding cell. We present gain-and loss-of-function analyses suggesting that DHCR7 functions as a negative regulator of Hh signaling at the level or downstream of Smoothened (Smo) and affects intracellular Hh signaling. Our analysis also raises the possibility that the human condition SLOS is caused not only by disruption of the enzymatic role of DHCR7 as a reductase in cholesterol biosynthesis, but may also involve defects in DHCR7 resulting in derepression of Shh signaling.

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Section: Plasmidsmentioning

confidence: 99%

Negative regulation of Hedgehog signaling by the cholesterogenic enzyme 7-dehydrocholesterol reductase

2006

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“…To gener-ate pBS-Xhairy2b∆W, pBS-Xhairy2b was cut with Eco47III/NcoI sites and blunted, followed by self-ligation. pCS2AT+-Myc-WRPW was constructed as described previously (Tsuji and Hashimoto, 2005). pCS2+-β-catenin was a kind gift from Dr. David Turner.…”

Section: Plasmid Constructionmentioning

confidence: 99%

Two modes of action by which Xenopus hairy2b establishes tissue demarcation in the Spemann-Mangold organizer

Murato¹,

Yamaguti²,

Katamura³

et al. 2006

Int. J. Dev. Biol.

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The Hairy and Enhancer-of-Split (HES) family of transcriptional repressors plays important roles in pattern formation during development throughout the animal kingdom. Generally, HES proteins repress the expression of genes specific for neighboring tissues to maintain the nature of cells expressing HES proteins, resulting in pattern formation. Xhairy2b, a Xenopus HES, establishes the prospective anterior prechordal mesoderm identity in the Spemann-Mangold organizer by both inducing specific genes and repressing the genes specific for neighboring tissues. Here we report that Xhairy2b has two modes of action, each of which corresponds to inductive and repressive functions. We show that the inductive function is independent of direct transcriptional regulation and is exhibited by the C-terminal WRPW tetrapeptide motif alone, although it induces the expression of a wide variety of the organizer genes that Xhairy2b represses. The transcriptional repression by Xhairy2b is responsible for only the repressive function. We propose that the activity of the WRPW motif intrinsically induces the expression of genes specific for the organizer in a rather non-specific manner to ensure the organizer environment. Then, the transcriptional repression selectively down-regulates the expression of some of these genes, resulting in the regionalization of the axial mesoderm. Our study provides new insight into how a region of the vertebrate embryo is demarcated by one dual-functional transcription factor in the early stages of development.

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“…Importantly, these studies implied a role for GRGs in Wnt-mediated dorsal-ventral (DV) patterning [50,51], one of the major early developmental decisions made in vertebrate embryos, that requires β-catenin accumulation and signaling activation [43,52–58]. …”

Section: Introductionmentioning

confidence: 99%

GRG5/AES Interacts with T-Cell Factor 4 (TCF4) and Downregulates Wnt Signaling in Human Cells and Zebrafish Embryos

et al. 2013

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Transcriptional control by TCF/LEF proteins is crucial in key developmental processes such as embryo polarity, tissue architecture and cell fate determination. TCFs associate with β-catenin to activate transcription in the presence of Wnt signaling, but in its absence act as repressors together with Groucho-family proteins (GRGs). TCF4 is critical in vertebrate intestinal epithelium, where TCF4-β-catenin complexes are necessary for the maintenance of a proliferative compartment, and their abnormal formation initiates tumorigenesis. However, the extent of TCF4-GRG complexes’ roles in development and the mechanisms by which they repress transcription are not completely understood. Here we characterize the interaction between TCF4 and GRG5/AES, a Groucho family member whose functional relationship with TCFs has been controversial. We map the core GRG interaction region in TCF4 to a 111-amino acid fragment and show that, in contrast to other GRGs, GRG5/AES-binding specifically depends on a 4-amino acid motif (LVPQ) present only in TCF3 and some TCF4 isoforms. We further demonstrate that GRG5/AES represses Wnt-mediated transcription both in human cells and zebrafish embryos. Importantly, we provide the first evidence of an inherent repressive function of GRG5/AES in dorsal-ventral patterning during early zebrafish embryogenesis. These results improve our understanding of TCF-GRG interactions, have significant implications for models of transcriptional repression by TCF-GRG complexes, and lay the groundwork for in depth direct assessment of the potential role of Groucho-family proteins in both normal and abnormal development.

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Choice of either β-catenin or Groucho/TLE as a co-factor for Xtcf-3 determines dorsal-ventral cell fate of diencephalon during Xenopus development

Cited by 12 publications

References 83 publications

Negative regulation of Hedgehog signaling by the cholesterogenic enzyme 7-dehydrocholesterol reductase

Negative regulation of Hedgehog signaling by the cholesterogenic enzyme 7-dehydrocholesterol reductase

Two modes of action by which Xenopus hairy2b establishes tissue demarcation in the Spemann-Mangold organizer

GRG5/AES Interacts with T-Cell Factor 4 (TCF4) and Downregulates Wnt Signaling in Human Cells and Zebrafish Embryos

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