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

@article{citeulike:3055204, abstract = {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.}, address = {Ecole Polytechnique F\'{e}d\'{e}rale de Lausanne (EPFL Institute for Experimental Cancer Research, School of Life Science, 1066 Epalinges, Switzerland.}, author = {Dubois, N. C. and Adolphe, C. and Ehninger, A. and Wang, R. A. and Robertson, E. J. and Trumpp, A.}, citeulike-article-id = {3055204}, citeulike-linkout-0 = {http://dx.doi.org/10.1242/dev.022707}, citeulike-linkout-1 = {http://dev.biologists.org/cgi/content/abstract/135/14/2455#FIG1}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18550708}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18550708}, doi = {10.1242/dev.022707}, issn = {0950-1991}, journal = {Development (Cambridge, England)}, keywords = {c-myc, placenta, sox2cre}, month = {July}, number = {14}, pages = {2455--2465}, posted-at = {2009-06-18 18:45:10}, priority = {2}, title = {Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function.}, url = {http://dx.doi.org/10.1242/dev.022707}, volume = {135}, year = {2008} }

TY - JOUR ID - citeulike:3055204 L3 - citeulike-article-id:3055204 N2 - 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. IS - 14 JF - Development (Cambridge, England) SN - 0950-1991 AD - Ecole Polytechnique Fédérale de Lausanne (EPFL Institute for Experimental Cancer Research, School of Life Science, 1066 Epalinges, Switzerland. EP - 2465 TI - Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function. VL - 135 SP - 2455 KW - c-myc KW - placenta KW - sox2cre AU - Dubois, NC AU - Adolphe, C AU - Ehninger, A AU - Wang, RA AU - Robertson, EJ AU - Trumpp, A PY - 2008/07// UR - http://dx.doi.org/10.1242/dev.022707 ER -