title: Redundant role of protein kinase C delta and epsilon during mouse embryonic development.
abstract: Protein Kinase C delta and epsilon are mediators of important cellular events, such as cell proliferation, migration or apoptosis. The formation of blood vessels, i.e., vasculo- and angiogenesis, is a process where these isoforms have also been shown to participate. However, mice deficient in either Protein Kinase C delta or epsilon are viable and therefore their individual contribution to the formation of the vasculature appeared so far dispensable. In this study, we show that double null mutation of Protein Kinase C delta and epsilon causes embryonic lethality at approximately E9.5. At this stage, whole mount staining of the endothelial marker CD31 in double null embryos revealed defective blood vessel formation. Moreover, culture of double deficient mouse allantois showed impaired endothelial cell organization, and analyses of double deficient embryo sections showed dilated vessels, decreased endothelial-specific adherent junctions, and decreased contact of endothelial cells with mural cells. Protein kinase C delta and epsilon also appeared essential for vascular smooth muscle cell differentiation, since α-smooth muscle actin, a classical marker for vascular smooth muscle cells, was almost undetectable in double deficient embryonic aorta at E9.5. Subsequent qPCR analyses showed decreased VE-cadherin, Vegfr2, Cd31, Cdh2, Ets1, and Fli-1, among other angiogenesis related transcripts in double deficient embryos. Taken together, these data suggest for the first time an in vivo redundant role between members of the novel Protein Kinase C subfamily that allows for mutual compensation during mouse embryonic development, with vasculogenesis/angiogenesis as an obvious common function of these two Protein Kinase Cs. Protein Kinase C delta and epsilon might therefore be useful targets for inhibiting vasculo- and/or angiogenesis.
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway.
authors.forename: Sergio
authors.initials: S
authors.lastname: Carracedo
authors.affiliation: Max Planck Institute of Experimental Endocrinology, Hannover, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Sacher
authors.affiliation: Zellbiologie im Zentrum Anatomie Gebäude I4, Raum, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Brandes
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway; Max Planck Institute of Experimental Endocrinology, Hannover, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Braun
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, Oslo, Norway; Max Planck Institute of Experimental Endocrinology, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011247:Pregnancy; D051745:Protein Kinase C-delta / Q000235:genetics / Q000502:physiology*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000502:physiology*; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D050784:Proto-Oncogene Protein c-ets-1; D051789:Proto-Oncogene Protein c-fli-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099152:Cadherin 5; C489083:Cdh2 protein, mouse; C494042:Ets1 protein, mouse; C497426:Fli1 protein, mouse; C000592875:Kdr protein, mouse
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