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Xenopus embryos lacking specific isoforms of the corepressor SMRT develop abnormal heads

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Xenopus embryos lacking specific isoforms of the corepressor SMRT develop abnormal heads. / Malartre, Marianne; Short, Stephen; Sharpe, Colin.

In: Developmental Biology, Vol. 292, No. 2, 15.04.2006, p. 333-343.

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Malartre, Marianne ; Short, Stephen ; Sharpe, Colin. / Xenopus embryos lacking specific isoforms of the corepressor SMRT develop abnormal heads. In: Developmental Biology. 2006 ; Vol. 292, No. 2. pp. 333-343.

Bibtex

@article{50e6deeca3bc46349d009934248fda7b,
title = "Xenopus embryos lacking specific isoforms of the corepressor SMRT develop abnormal heads",
abstract = "The corepressor SMRT acts on a range of transcription factors, including the retinoid and thyroid hormone nuclear receptors. The carboxy-terminal region of SMRT contains CoRNR box motifs that mediate these interactions. We have shown, in Xenopus, that SMRT can exist as isoforms containing either two or three CoRNR boxes depending on the alternative splicing of exon 37b. The number of SMRT transcript isoforms expressed increases during development until all sixteen possible isoforms are identified in the swimming tadpole. To eliminate specific SMRT isoforms, we have developed a process that uses an antisense morpholino oligonucleotide in Xenopus to dictate the outcome of alternative splicing at a defined exon and used this to inhibit the formation of transcripts containing exon 37b. These embryos are therefore limited to the expression of SMRT isoforms that contain two rather than three CoRNR boxes. Analysis of responsive genes in these embryos shows that targets of thyroid hormone, but not retinoid signaling are affected by the elimination of exon 37b. Morpholino-injected embryos have swimming abnormalities and develop altered head morphology, an expanded olfactory epithelium and disorganized peripheral axons. These experiments indicate a critical role for the alternative splicing of SMRT in development.",
keywords = "Alternative Splicing, Animals, Embryo, Nonmammalian, Exons, Gastrula, Gene Expression Profiling, Gene Expression Regulation, Developmental, Head, In Situ Hybridization, Oligonucleotides, Antisense, Protein Isoforms, RNA, Messenger, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic, Xenopus, Xenopus Proteins",
author = "Marianne Malartre and Stephen Short and Colin Sharpe",
year = "2006",
month = apr,
day = "15",
doi = "10.1016/j.ydbio.2006.01.007",
language = "English",
volume = "292",
pages = "333--343",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Xenopus embryos lacking specific isoforms of the corepressor SMRT develop abnormal heads

AU - Malartre, Marianne

AU - Short, Stephen

AU - Sharpe, Colin

PY - 2006/4/15

Y1 - 2006/4/15

N2 - The corepressor SMRT acts on a range of transcription factors, including the retinoid and thyroid hormone nuclear receptors. The carboxy-terminal region of SMRT contains CoRNR box motifs that mediate these interactions. We have shown, in Xenopus, that SMRT can exist as isoforms containing either two or three CoRNR boxes depending on the alternative splicing of exon 37b. The number of SMRT transcript isoforms expressed increases during development until all sixteen possible isoforms are identified in the swimming tadpole. To eliminate specific SMRT isoforms, we have developed a process that uses an antisense morpholino oligonucleotide in Xenopus to dictate the outcome of alternative splicing at a defined exon and used this to inhibit the formation of transcripts containing exon 37b. These embryos are therefore limited to the expression of SMRT isoforms that contain two rather than three CoRNR boxes. Analysis of responsive genes in these embryos shows that targets of thyroid hormone, but not retinoid signaling are affected by the elimination of exon 37b. Morpholino-injected embryos have swimming abnormalities and develop altered head morphology, an expanded olfactory epithelium and disorganized peripheral axons. These experiments indicate a critical role for the alternative splicing of SMRT in development.

AB - The corepressor SMRT acts on a range of transcription factors, including the retinoid and thyroid hormone nuclear receptors. The carboxy-terminal region of SMRT contains CoRNR box motifs that mediate these interactions. We have shown, in Xenopus, that SMRT can exist as isoforms containing either two or three CoRNR boxes depending on the alternative splicing of exon 37b. The number of SMRT transcript isoforms expressed increases during development until all sixteen possible isoforms are identified in the swimming tadpole. To eliminate specific SMRT isoforms, we have developed a process that uses an antisense morpholino oligonucleotide in Xenopus to dictate the outcome of alternative splicing at a defined exon and used this to inhibit the formation of transcripts containing exon 37b. These embryos are therefore limited to the expression of SMRT isoforms that contain two rather than three CoRNR boxes. Analysis of responsive genes in these embryos shows that targets of thyroid hormone, but not retinoid signaling are affected by the elimination of exon 37b. Morpholino-injected embryos have swimming abnormalities and develop altered head morphology, an expanded olfactory epithelium and disorganized peripheral axons. These experiments indicate a critical role for the alternative splicing of SMRT in development.

KW - Alternative Splicing

KW - Animals

KW - Embryo, Nonmammalian

KW - Exons

KW - Gastrula

KW - Gene Expression Profiling

KW - Gene Expression Regulation, Developmental

KW - Head

KW - In Situ Hybridization

KW - Oligonucleotides, Antisense

KW - Protein Isoforms

KW - RNA, Messenger

KW - Repressor Proteins

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Transcription, Genetic

KW - Xenopus

KW - Xenopus Proteins

UR - https://www.sciencedirect.com/science/article/pii/S0012160606000170?via%3Dihub

U2 - 10.1016/j.ydbio.2006.01.007

DO - 10.1016/j.ydbio.2006.01.007

M3 - Article

C2 - 16500640

VL - 292

SP - 333

EP - 343

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -

ID: 696888