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.

journal_name

Dev Biol

journal_title

Developmental biology

authors

Malartre M,Short S,Sharpe C

doi

10.1016/j.ydbio.2006.01.007

subject

Has Abstract

pub_date

2006-04-15 00:00:00

pages

333-43

issue

2

eissn

0012-1606

issn

1095-564X

pii

S0012-1606(06)00017-0

journal_volume

292

pub_type

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