Brief reviewsMesp1 Expression Is the Earliest Sign of Cardiovascular Development
Section snippets
Mesp1 Is Expressed in the Early Mesoderm and Involved in Cardiac Morphogenesis
Mesp1, belonging to the bHLH transcription factor family, is expressed in the early mesoderm at the onset of gastrulation (Figure 1 and Saga et al. 1996). The expression of the transcript is restricted to a part of mesoderm ingressed through the primitive streak of the early stage embryo (6.5–7.0 dpc) and quickly down-regulated after 7.5 dpc and no expression has been observed in the paraxial or axial mesoderm. Only the slight expression observed at a later stage embryo (8.5 dpc in Figure 1)
Mesp1-Expressing Cell Lineage
Cell type-specific genomic alternations mediated by the (Figure 2) Cre/loxP system constitute a powerful approach to the study of cell lineages Trainor et al. 1999, Yamauchi et al. 1999, Zinyk et al. 1998. On crossing heterozygous Mesp1-Cre and reporter mice CAG-CAT-Z, one quarter of the progeny should consist of double transgenics (Figure 2A). Only cells that express Cre from the Mesp1 allele should undergo recombination between the loxP sites of the reporter construct, excising the CAT gene
Mesp1, Mesp2 Double Knockout Mouse
The abnormal heart morphogenesis in Mesp1 (−/−) embryos resulting in cardia bifida is caused by delayed migration of the cardiac precursor cells. However, the initial suppression of cell migration is rescued at the later stages and the Mesp1 (−/−) embryo eventually generates an abnormal heart tube. The involvement of Mesp2, another gene of the same family, is indicated because of the similar expression pattern. An early expression study did not reveal Mesp2 expression at the early stage embryo,
Chimera Analysis Reveals Cell-autonomous Function of Mesp1 and Mesp2 in Cardiac Morphogenesis
Mesp1 and Mesp2 are expressed only in the early ingressed group of mesoderm and not in the paraxial and axial mesoderm. No paraxial mesoderm was generated in the dKO embryo, which resulted in a complete lack of somites. To clarify whether such mesodermal defects observed in the Mesp1,p2-dKO embryo are of a cell-autonomous or non-cell-autonomous consequence, chimera analysis was conducted (see Figure 4 for the method). A chimeric embryo was generated by aggregating 8-cell embryos derived from
Discussion
Mesodermal cells generate the heart tube. The embryonic mesoderm can be divided into five regions; the chorda (axial) mesoderm, somitic dorsal (paraxial) mesoderm, intermediate mesoderm, lateral plate mesoderm, and head mesenchyme (Gilbert 2000). It is generally thought that the heart is derived from the lateral plate mesoderm. The results of our experiments and fate mapping studies (Tam et al. 2000) showed that the heart precursors in mouse are clearly localized as the cranial-cardiac mesoderm
Conclusion
The series of experiments described here involving cell lineage, loss of function and chimeric analyses revealed a differential requirement of Mesp1 and Mesp2 for different cell lineages. For the extraembryonic mesoderm, lack of Mesp1 and Mesp2 did not result in a severe defect in either mesodermal formation or subsequent cell differentiation, suggesting that these genes may not be required for extraembryonic mesoderm development or, alternatively, other molecules may rescue the deficiency of
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2020, Cell ReportsCitation Excerpt :Mice homozygous for a Prdm16 allele with two loxP sites flanking exon 9 were crossed with heterozygous mice that express the Mesp1Cre transgene (Harms et al., 2014; Saga et al., 1999). Because Prdm16 is expressed in most cardiac cell types during development, we decided to use the Mesp1Cre line, which is active at onset of gastrulation and drives Cre recombinase activity in cardiogenic progenitors that give rise to all cell types in the cardiovascular system (Figure 1A; Saga et al., 1999, 2000;). To determine the efficiency of the Prdm16 deletion, we performed qPCR analysis on heart tissues harvested from control and cKO mice.