Embryonic arrest at midgestation and disruption of Notch signaling produced by the absence of both epsin 1 and epsin 2 in mice

Hong Chen, Genevieve Ko, Alessandra Zatti, Giuseppina Di Giacomo, Lijuan Liu, Elisabetta Raiteri, Ezio Perucco, Chiara Collesi, Wang Min, Caroline Zeiss, Pietro De Camilli, Ottavio Cremona

Research output: Contribution to journalArticlepeer-review

Abstract

Epsins are endocytic adaptors with putative functions in general aspects of clathrin-mediated endocytosis as well as in the internalization of specific membrane proteins. We have now tested the role of the ubiquitously expressed epsin genes, Epn1 and Epn2, by a genetic approach in mice. While either gene is dispensable for life, their combined inactivation results in embryonic lethality at E9.5-E10, i.e., at the beginning of organogenesis. Consistent with studies in Drosophila, where epsin endocytic function was linked to Notch activation, developmental defects observed in epsin 1/2 double knockout (DKO) embryos recapitulated those produced by a global impairment of Notch signaling. Accordingly, expression of Notch primary target genes was severely reduced in DKO embryos. However, housekeeping forms of clathrin-mediated endocytosis were not impaired in cells derived from these embryos. These findings support a role of epsin as a specialized endocytic adaptor, with a critical role in the activation of Notch signaling in mammals.

Original languageEnglish
Pages (from-to)13838-13843
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number33
DOIs
Publication statusPublished - Aug 18 2009

Keywords

  • Cell signaling
  • Endocytosis
  • Gene targeting

ASJC Scopus subject areas

  • General

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