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in vitro studies have suggested an indispensable role for TGF-β-signaling in differentiation of NCCs into smooth muscle cells. Moreover, a recent in vivo study suggested that mice lacking Tgfbr2 in CNCCs display defective NCC differentiation into αSMA-positive cells in the AP septum [9], although this result was later disputed by another study [8]. Our immunohistochemical staining of αSMA in the OFT unequivocally demonstrated that signaling via ALK5 is not required for smooth muscle differentiation in vivo. Moreover, it has been suggested that deletion of Tgfbr2 in NCCs leads to other phenotypic features reminiscent of those seen in the velocardiofacial/DiGeorge syndrome (VCF/DGS) [9] caused by a deletion of the so called DiGeorge critical region (DGCR) on chromosome 22q11 [34,35]. Our present results suggest that although many of the observed phenotypes seen in Alk5/Wnt1-Cre mutants superficially resemble those seen in VCF/DGS, a detailed examination shows that the NC-specific abrogation of Alk5 does not lead to VCF/DGS-like phenotypes. Firstly, while the pharyngeal organ migration fails in Alk5/Wnt1-Cre mutants, perhaps as a result of increased mesenchymal cell death in the pharyngeal region, both the thymus, thyroid and parathyroid seem to develop relatively normally on the histological level in these mutants. Secondly, the NCC death seen in Alk5 mutants affects a predominantly postmigratory population of NCCs, while genes located in the DGCR, i.e., Tbx1 and CrkL, control NCC survival earlier at E8.5-E10 by regulating proliferation of the secondary heart field (SHF), and endoderm expansion, which in turn provides survival signal for NCCs allowing them to populate the pharyngeal region [36-39]."}

    craft-ca-core-ex-dev

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in vitro studies have suggested an indispensable role for TGF-β-signaling in differentiation of NCCs into smooth muscle cells. Moreover, a recent in vivo study suggested that mice lacking Tgfbr2 in CNCCs display defective NCC differentiation into αSMA-positive cells in the AP septum [9], although this result was later disputed by another study [8]. Our immunohistochemical staining of αSMA in the OFT unequivocally demonstrated that signaling via ALK5 is not required for smooth muscle differentiation in vivo. Moreover, it has been suggested that deletion of Tgfbr2 in NCCs leads to other phenotypic features reminiscent of those seen in the velocardiofacial/DiGeorge syndrome (VCF/DGS) [9] caused by a deletion of the so called DiGeorge critical region (DGCR) on chromosome 22q11 [34,35]. Our present results suggest that although many of the observed phenotypes seen in Alk5/Wnt1-Cre mutants superficially resemble those seen in VCF/DGS, a detailed examination shows that the NC-specific abrogation of Alk5 does not lead to VCF/DGS-like phenotypes. Firstly, while the pharyngeal organ migration fails in Alk5/Wnt1-Cre mutants, perhaps as a result of increased mesenchymal cell death in the pharyngeal region, both the thymus, thyroid and parathyroid seem to develop relatively normally on the histological level in these mutants. Secondly, the NCC death seen in Alk5 mutants affects a predominantly postmigratory population of NCCs, while genes located in the DGCR, i.e., Tbx1 and CrkL, control NCC survival earlier at E8.5-E10 by regulating proliferation of the secondary heart field (SHF), and endoderm expansion, which in turn provides survival signal for NCCs allowing them to populate the pharyngeal region [36-39]."}

    craft-ca-core-dev

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