{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T12:56:09Z","timestamp":1761742569986},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,2,6]],"date-time":"2005-02-06T00:00:00Z","timestamp":1107648000000},"content-version":"vor","delay-in-days":4419,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev. Genet."],"published-print":{"date-parts":[[1993,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In a search for functions of transforming growth factor\u2010\u03b2 during early embryonic development we used two different experimental approaches. In the first we made use of embryonic stem (ES) cells. ES cells in culture differentiate to derivatives of all three germ layers and mimic some aspects of organogenesis when grown as aggregates in suspension to form embryoid bodies. Differentiation procedes further when the embryold bodies attach to suitable substrates. Muscle and neuronal cells are among the most readily identified cell types then formed. We examined the effect of all\u2010trans retinoic acid (RA) and members of the transforming growth factor\u2010\u03b2 family(TGF\u2010\u03b2l, TGF\u2010\u03b22) under these conditions in an assay where single aggregates formed in hanging microdrops in medium supplemented with serum depleted of lipophilic substances which would include retinoids. Endoderm\u2010like cells formed under all conditions tested. RA at concentrations of 10<jats:sup>8<\/jats:sup> M and 10<jats:sup>7<\/jats:sup> M induced the formation of neurons but in the absence of RA or at concentrations up to 10\u2212<jats:sup>9<\/jats:sup> M, neurons were not observed. Instead, beating muscle formed in about one\u2010third of the plated aggregates; this was greatly reduced when RA concentrations increased above 10\u2212<jats:sup>9<\/jats:sup> M. Immunofluorescent staining for muscle specific myosin showed that two muscle cell types could be distinguished: elongated, non\u2010contractile myoblasts and mononucleate flat cells. The mononucleate flat cells appeared to correspond with rhythmically contracting muscle. The number of non\u2010contractile myoblasts increased 3\u2010fold over controls in the presence of 10\u2212<jats:sup>9<\/jats:sup> M RA. TGF\u2010\u03b2s increased the number of contractile and non\u2010contractile muscle cells by a factor 3 to 7 over controls, depending on the TGF\u2010\u03b2 isoform added and the muscle cell type formed. TGF\u2010\u03b22 also invariably increased the rate at which contracting muscle cells were first observed in replated aggregates. The stimulatory effect of TGF\u2010\u03b2s on the formation of mononucleate flat cells was completely abrogated by RA at 10\u2212<jats:sup>9<\/jats:sup> M while the number of myoblasts under similar conditions was unchanged. These data suggest that a complex interplay between retinoids and TGF\u2010\u03b2 isoforms may be involved in regulation of differentiation in early myogenesis.<\/jats:p><jats:p>In the second approach, neutralizing polyclonal rabbit antibodies specific for TGF\u2010\u03b22 were injected into the cavity of mouse blastocysts 3.5 days post coitum (pc). After 1 day in culture, embryos were transferred to pseudopregnant females. The number of decidua, embryos and resorptions were counted at day 8.5\u20139.5 pc. Control antibody injected embryos implanted with high efficiency (87%) compared with anti\u2010TGF\u2010\u03b22 injected embryos which implanted with an efficiency of only 43%. If empty decidua (resorptions) were included, the overall recovery was 71% and 32% for control and experimental embryos, respectively. Embryos that were recovered showed no overt macroscopic abnormalities. These results together impiy functions for TGF\u2010\u03b2s in implantation as well as in later development of the embryo. \u00a9 1993Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvg.1020140308","type":"journal-article","created":{"date-parts":[[2005,5,25]],"date-time":"2005-05-25T22:36:31Z","timestamp":1117060591000},"page":"212-224","source":"Crossref","is-referenced-by-count":60,"title":["Transforming growth factor\u2010\u03b2 in the early mouse embryo: Implications for the regulation of muscle formation and implantation"],"prefix":"10.1002","volume":"14","author":[{"given":"H. 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