Early embryonic hematopoiesis in mammals is defined by three successive waves of hematopoietic progenitors which exhibit a distinct hematopoietic potential and provide continuous support for the development of the embryo and adult organism. Although the functional importance of each of these waves has been analyzed, their spatio-temporal overlap and the lack of wave-specific markers hinders the accurate separation and assessment of their functional roles during early embryogenesis. We have recently shown that TLR2, in combination with c-kit, represents the earliest signature of emerging precursors of the second hematopoietic wave, erythro-myeloid precursors (EMPs). Since the onset of Tlr2 expression distinguishes EMPs from primitive progenitors which coexist in the yolk sac from E7.5, we generated a novel transgenic "knock in" mouse model, Tlr2Dtr , suitable for inducible targeted depletion of TLR2+ EMPs. In this model, the red fluorescent protein and diphtheria toxin receptor sequences are linked via a P2A sequence and inserted into the Tlr2 locus before its stop codon. We show that a timely controlled deletion of TLR2+ EMPs in Tlr2Dtr embryos results in a marked decrease in both erythroid as well as myeloid lineages and, consequently, in embryonic lethality peaking before E13.5. These findings validate the importance of EMPs in embryonic development.

• MeSH
• embryo savčí embryologie   patologie   MeSH
• embryonální vývoj genetika   MeSH
• erytrocyty cytologie   MeSH
• hematopoéza genetika   fyziologie   MeSH
• makrofágy cytologie   MeSH
• myeloidní progenitorové buňky cytologie   MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• toll-like receptor 2 genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• homologní transplantace metody   statistika a číselné údaje   trendy   MeSH
• lidé MeSH
• myeloidní progenitorové buňky cytologie   imunologie   transplantace   MeSH
• myeloproliferativní poruchy klasifikace   MeSH
• primární myelofibróza diagnóza   etiologie   terapie   MeSH
• trombocytopenie farmakoterapie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• srovnávací studie MeSH