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First published online 30 November 2006
doi: 10.1242/dev.02722

Development 134, 31-41 (2007)
Published by The Company of Biologists 2007
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Gene replacement reveals a specific role for E-cadherin in the formation of a functional trophectoderm

Natalia G. Kan1,*, Marc P. Stemmler1, Dirk Junghans1, Benoît Kanzler1, Wilhelmine N. de Vries2, Mara Dominis3 and Rolf Kemler1,{dagger}

1 Max-Planck-Institut für Immunbiologie, Abteilung für Molekulare Embryologie, Stübeweg 51, D-79108 Freiburg, Germany.
2 The Jackson Laboratory, Bar Harbor, ME 04609-1500, USA.
3 Department of Pathology, Clinical Hospital Merkur, 4100 Zagreb, Croatia.

{dagger} Author for correspondence (e-mail: Kemler{at}immunbio.mpg.de)

Accepted 27 October 2006

During mammalian embryogenesis the trophectoderm represents the first epithelial structure formed. The cell adhesion molecule E-cadherin is ultimately necessary for the transition from compacted morula to the formation of the blastocyst to ensure correct establishment of adhesion junctions in the trophectoderm. Here, we analyzed to what extent E-cadherin confers unique adhesion and signaling properties in trophectoderm formation in vivo. Using a gene replacement approach, we introduced N-cadherin cDNA into the E-cadherin genomic locus. We show that the expression of N-cadherin driven from the E-cadherin locus reflects the expression pattern of endogenous E-cadherin. Heterozygous mice co-expressing E- and N-cadherin are vital and show normal embryonic development. Interestingly, N-cadherin homozygous mutant embryos phenocopy E-cadherin-null mutant embryos. Upon removal of the maternal E-cadherin, we demonstrate that N-cadherin is able to provide sufficient cellular adhesion to mediate morula compaction, but is insufficient for the subsequent formation of a fully polarized functional trophectoderm. When ES cells were isolated from N-cadherin homozygous mutant embryos and teratomas were produced, these ES cells differentiated into a large variety of tissue-like structures. Importantly, different epithelial-like structures expressing N-cadherin were formed, including respiratory epithelia, squamous epithelia with signs of keratinization and secretory epithelia with goblet cells. Thus, N-cadherin can maintain epithelia in differentiating ES cells, but not during the formation of the trophectoderm. Our results point to a specific and unique function for E-cadherin during mouse preimplantation development.

Key words: E-cadherin, N-cadherin, Trophectoderm formation, Cell adhesion, Gene replacement, Mouse




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R. Yagi, M. J. Kohn, I. Karavanova, K. J. Kaneko, D. Vullhorst, M. L. DePamphilis, and A. Buonanno
Transcription factor TEAD4 specifies the trophectoderm lineage at the beginning of mammalian development
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[Abstract] [Full Text] [PDF]


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