Restricted expression of ETn-related sequences during post-implantation mouse development

Loebel, David A.F.; Tsoi, Bonny; Wong, Nicole; O'Rourke, Meredith P.; Tam, Patrick

doi:10.1016/j.modgep.2003.12.003

Cited by 24 publications

(25 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). Expression was observed in both fore-and hindlimb buds and confined to the mesenchyme in WT embryos, as reported previously (18). Interestingly, heterozygous dactylaplasia mutant (Dac 1J /ϩ mdac/mdac) embryos exhibited aberrant MusD expression at the central portion of the apical ectodermal ridge (AER) in addition to its normal expression.…”

Section: Ectopic Expression Of Musd Elements In Dactylaplasia Mutant supporting

confidence: 81%

“…Recently, a tissue-and stage-specific expression pattern for MusD and ETn elements has been shown in organogenesis-stage mouse embryos (18). To examine the MusD expression pattern in dactylaplasia mice, we generated a MusD antisense strand probe from the 3Ј UTR region of the MusD element for hybridization to embryos in various developmental stages [embryonic day (E)9.5-E11.5] (Fig.…”

Section: Ectopic Expression Of Musd Elements In Dactylaplasia Mutant mentioning

confidence: 99%

See 1 more Smart Citation

Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype

Kano

Kurahashi

Toda

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Dactylaplasia, characterized by missing central digital rays, is an inherited mouse limb malformation that depends on two genetic loci. The first locus, Dac, is an insertional mutation around the dactylin gene that is inherited as a semidominant trait. The second locus is an unlinked modifier, mdac/Mdac, that is polymorphic among inbred strains. Mdac dominantly suppresses the dactylaplasia phenotype in mice carrying Dac. However, little is known about either locus or the nature of their interaction. Here we show that Dac is a LTR retrotransposon insertion caused by the type D mouse endogenous provirus element (MusD). This insertion exhibits different epigenetic states and spatiotemporally expresses depending on the mdac/Mdac modifier background. In dactylaplasia mutants (Dac/؉ mdac/mdac), the LTRs of the insertion contained unmethylated CpGs and active chromatin. Furthermore, MusD elements expressed ectopically at the apical ectodermal ridge of limb buds, accompanying the dactylaplasia phenotype. On the other hand, in Dac mutants carrying Mdac (Dac/؉ Mdac/mdac), the 5 LTR of the insertion was heavily methylated and enriched with inactive chromatin, correlating with inhibition of the dactylaplasia phenotype. Ectopic expression was not observed in the presence of Mdac, which we refined to a 9.4-Mb region on mouse chromosome 13. We report a pathogenic mutation caused by MusD. Our findings indicate that ectopic expression from the MusD insertion correlates with the dactylaplasia phenotype and that Mdac acts as a defensive factor to protect the host genome from pathogenic MusD insertions.dactylin ͉ ectrodactyly ͉ LTR ͉ split hand/split foot malformation ͉ methylation D actylaplasia is an inherited mouse limb malformation that is characterized by missing central digital rays. The Dac mutation is inherited as a semidominant trait, evidenced by missing central digits in the fore-and hindlimbs of heterozygous mice and monodactyly in homozygous mice (1, 2). The Dac locus has been mapped to the distal end of chromosome 19. Two independent Dac mutant alleles, Dac 1J and Dac 2J , arose spontaneously in breeding colonies. Both are insertions residing within the same locus: Dac 1J is located in the region upstream of the dactylin gene, and Dac 2J is located in intron 5 of dactylin (3). Southern blot analysis indicated that both insertions are larger than 4.5 kb; however, ''jumping PCR'' identified only the LTR portion of the insertion (3). Partial PCR products terminating in the 5Ј and 3Ј LTRs cross-prime each other, resulting in amplified products that lack any of the internal sequence between LTRs. Therefore, these insertions were thought to be caused by an early transposon (ETn) element, which is a common mutagen in mice (4, 5).Split hand/split foot malformation (SHFM) in humans is a congenital limb malformation that has an ectrodactyly phenotype analogous to that of the dactylaplasia mouse. SHFM is genetically heterogeneous; to date, five different loci, SHFM1 to SHFM5, have been mapped. Dactylaplasia is a mouse model of S...

show abstract

Section: Ectopic Expression Of Musd Elements In Dactylaplasia Mutant supporting

confidence: 81%

Section: Ectopic Expression Of Musd Elements In Dactylaplasia Mutant mentioning

confidence: 99%

Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype

Kano

Kurahashi

Toda

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Automated whole-mount in situ hybridization was carried out on an InSituPro machine (AbiMed) using a published protocol (Wilkinson and Nieto, 1993) modified as described previously (Loebel et al, 2004) and stained with BM purple (Roche). Antisense riboprobes were generated from linearized plasmids for Apom and Pax9, or plasmid inserts amplified with M13 forward and reverse primers for Rhou (IMAGE clone 3964150), Igfbp5 (IMAGE clone 2648602), Cldn4 (IMAGE clone 876728).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Rhou maintains the epithelial architecture and facilitates differentiation of the foregut endoderm

et al. 2011

View full text Add to dashboard Cite

SUMMARYRhou encodes a Cdc42-related atypical Rho GTPase that influences actin organization in cultured cells. In mouse embryos at earlysomite to early-organogenesis stages, Rhou is expressed in the columnar endoderm epithelium lining the lateral and ventral wall of the anterior intestinal portal. During foregut development, Rhou is downregulated in regions where the epithelium acquires a multilayered morphology heralding the budding of organ primordia. In embryos generated from Rhou knockdown embryonic stem (ES) cells, the embryonic foregut displays an abnormally flattened shape. The epithelial architecture of the endoderm is disrupted, the cells are depleted of microvilli and the phalloidin-stained F-actin content of their sub-apical cortical domain is reduced. Rhou-deficient cells in ES cell-derived embryos and embryoid bodies are less efficient in endoderm differentiation. Impaired endoderm differentiation of Rhou-deficient ES cells is accompanied by reduced expression of c-Jun/AP-1 target genes, consistent with a role for Rhou in regulating JNK activity. Downregulation of Rhou in individual endoderm cells results in a reduced ability of these cells to occupy the apical territory of the epithelium. Our findings highlight epithelial morphogenesis as a required intermediate step in the differentiation of endoderm progenitors. In vivo, Rhou activity maintains the epithelial architecture of the endoderm progenitors, and its downregulation accompanies the transition of the columnar epithelium in the embryonic foregut to a multilayered cell sheet during organ formation.

show abstract

“…These small RNAs are of the same size as siRNAs but are independent of Dicer function. Among them, one particularly abundant Dicer-independent small RNA corresponds to the ETn/MusD family known to be transcriptionally active during early embryogenesis [22,131,132], though significance of this finding is not yet clear. This small RNA is antisense to the primer-binding site of ETn/MusD, and thus it cannot be excluded that it is a degradation product of the tRNA that serves as a primer during reverse transcription of these elements, rather than a regulatory RNA.…”

Section: Regulation Of Ltr-retroelements By Small Rnasmentioning

confidence: 99%

Endogenous retroviruses

Maksakova

Mager

Reiss

2008

Cell. Mol. Life Sci.

150

View full text Add to dashboard Cite

Endogenous retrovirus-like elements, or ERVs, are an abundant component of all eukaryotic genomes. Their transcriptional and retrotranspositional activities have great potential for deleterious effects on gene expression. Consequences of such activity may include germline mutagenesis and cancerous transformation. As a result, mammalian genomes have evolved means of counteracting ERV transcription and mobilization. In this review, we discuss epigenetic mechanisms of ERV and LTR retrotransposon control during mouse development, focusing on involvement of DNA methylation, histone modifications, small RNAs and their interaction with one another. We also address relevance of research performed in the mouse system to human and challenges associated with studying repetitive families. (Part of a multi-author review).

show abstract

Restricted expression of ETn-related sequences during post-implantation mouse development

Cited by 24 publications

References 11 publications

Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype

Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype

Rhou maintains the epithelial architecture and facilitates differentiation of the foregut endoderm

Endogenous retroviruses

Contact Info

Product

Resources

About