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First published online 11 June 2008
doi: 10.1242/dev.022707

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.022707v1 135/14/2455    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Dubois, N. C. Articles by Trumpp, A. PubMed PubMed Citation Articles by Dubois, N. C. Articles by Trumpp, A.

Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function

Nicole C. Dubois^1,*, Christelle Adolphe¹, Armin Ehninger¹, Rong A. Wang², Elisabeth J. Robertson³ and Andreas Trumpp^1,

¹ Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, School of Life Science, 1066 Epalinges, Switzerland.
² Pacific Vascular Research Laboratory, Division of Vascular Surgery, Department of Surgery, University of California, San Francisco, CA 94143, USA.
³ Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.

Author for correspondence (e-mail: andreas.trumpp{at}epfl.ch)

Accepted 29 April 2008

The c-Myc protein has been implicated in playing a pivotal role in regulating the expression of a large number of genes involved in many aspects of cellular function. Consistent with this view, embryos lacking the c-myc gene exhibit severe developmental defects and die before midgestation. Here, we show that Sox2Cre-mediated deletion of the conditional c-myc^flox allele specifically in the epiblast (hence trophoectoderm and primitive endoderm structures are wild type) rescues the majority of developmental abnormalities previously characterized in c-myc knockout embryos, indicating that they are secondary defects and arise as a result of placental insufficiency. Epiblast-restricted c-Myc-null embryos appear morphologically normal and do not exhibit any obvious proliferation defects. Nonetheless, these embryos are severely anemic and die before E12. c-Myc-deficient embryos exhibit fetal liver hypoplasia, apoptosis of erythrocyte precursors and functionally defective definitive hematopoietic stem/progenitor cells. Specific deletion of c-myc^flox in hemogenic or hepatocytic lineages validate the hematopoietic-specific requirement of c-Myc in the embryo proper and provide in vivo evidence to support a synergism between hematopoietic and liver development. Our results reveal for the first time that physiological levels of c-Myc are essential for cell survival and demonstrate that, in contrast to most other embryonic lineages, erythroblasts and hematopoietic stem/progenitor cells are particularly dependent on c-Myc function.

Key words: c-Myc, Hematopoietic stem cell, Placenta, Embryonic hematopoiesis, Fetal liver, Survival, Mouse

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c-Myc essential for haematopoiesis

Development 2008 135: e1404. [Full Text]  

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