Elsevier

Developmental Biology

Volume 228, Issue 2, 15 December 2000, Pages 315-325
Developmental Biology

Regular Article
Acidic Endomembrane Organelles Are Required for Mouse Postimplantation Development

https://doi.org/10.1006/dbio.2000.9963Get rights and content
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Abstract

Vacuolar-type H+-ATPase (V-ATPase) plays a major role in endomembrane and plasma membrane proton transport in eukaryotes. We found that the acidic compartments generated by V-ATPase are present from the one-cell stage of mouse preimplantation embryos. Upon differentiation of trophoblasts and the inner cell mass at the blastocyst stage, these compartments exhibited a polarized perinuclear distribution. PL16−/− embryos, lacking the V-ATPase 16-kDa proteolipid (c subunit), developed to the blastocyst stage and were implanted in the uterine epithelium, but died shortly thereafter. This mutant showed severe defects in development of the embryonic and extraembryonic tissues at a stage that coincided with rapid cell proliferation. When cultured in vitro, PL16−/− blastocysts could hatch and become attached to the surface of a culture dish, but the inner cell mass grew significantly slower and most cells failed to survive for more than 4 days. PL16−/− cells showed impaired endocytosis as well as organellar acidification. The Golgi complex became swollen and vacuolated, possibly due to the absence of the luminal acidic pH. These results clearly indicate that acidic compartments are essential for development after implantation.

Keywords

V-ATPase
proteolipid
luminal acidic compartments
mammalian early development
knockout mice

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This work was supported in part by grants from the Ministry of Education, Science, and Culture of Japan.

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