HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 2, 1109-1118, January 12, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/2/1109    most recent M606535200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Liu, C.-L. Articles by Hsu, H.-C. Search for Related Content PubMed PubMed Citation Articles by Liu, C.-L. Articles by Hsu, H.-C. Social Bookmarking                      What's this?

L2dtl Is Essential for Cell Survival and Nuclear Division in Early Mouse Embryonic Development^*

Chao-Lien Liu, I-Shing Yu, Hung-Wei Pan, Shu-Wha Lin^¶1, and Hey-Chi Hsu^||2

From the Graduate Institute of Pathology and Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, and the Departments of ^¶Laboratory Medicine and ^||Pathology, National Taiwan University Hospital, National Taiwan University, Taipei 100, Taiwan

l(2)dtl (lethal (2) denticleless), is an embryonic lethal homozygous mutation initially identified in Drosophila melanogaster that produces embryos that lack ventral denticle belts. In addition to nucleotide sequence, bioinformatic analysis has revealed a conservation of critical functional motifs among the human L2DTL, mouse L2dtl, and Drosophila l(2)dtl proteins. The function of the L2DTL protein in the development of mammalian embryos was studied using targeted disruption of the L2dtl gene in mice. The knock-out resulted in early embryonic lethality. L2dtl^-/- embryos were deformed and terminated development at the 4–8-cell stage. Microinjection of a small interfering RNA (siRNA) vector (siRNA-L2dtl) into the two-cell stage nuclei of wild-type mouse embryos led to cell cycle progression failure, termination of cell division, and, eventually, embryonic death during the preimplantation stage. Morphological studies of the embryos 54 h after injection showed fragmentation of mitotic chromosomes and chromosomal lagging, hallmarks of mitotic catastrophe. The siRNA-L2dtl-treated embryos eventually lysed and failed to develop into blastocysts after 72 h of in vitro culturing. However, the embryos developed normally after they were microinjected into one nucleus of the two-celled embryos. The siRNA studies in HeLa cells showed that L2dtl protein depletion results in multinucleation and down-regulation of phosphatidylinositol 3-kinase, proliferating cell nuclear antigen, and PTTG1/securin, which might partially explain the mitotic catastrophe observed in L2dtl-depleted mouse embryos. Based on these findings, we conclude that L2dtl gene expression is essential for very early mouse embryonic development.

Received for publication, July 10, 2006 , and in revised form, October 13, 2006.

^* This work was supported by National Science Council of the Republic of China Grants NSC93-2320-B002-108 and NHRI-EX94-9427NI (to H. C. H.) and National Science Council, National Taiwan University Hospital and National Health Research Institute, Department of Health, the Republic of China (Taipei, Taiwan) Grants NSC94-3112-B002-014, NSC95-3112-B002-017, and 91-B-FA09-2-4 and 90A01–91A06 (to S. W. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence and reprint requests may be addressed: Dept. of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan. Fax: 886-2-23817083; E-mail: swlin{at}ha.mc.ntu.edu.tw. ² To whom correspondence and reprint requests may be addressed: Dept. of Pathology, National Taiwan University Hospital, Taipei 100, Taiwan. Fax: 886-2-23410876; E-mail: heychi{at}ha.mc.ntu.edu.tw.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?