Possible roles for TGF beta 1 in the gastrulating chick embryo.
We have examined the immunocytochemical distribution of TGF beta 1 (transforming growth factor beta 1) in the gastrulating chick embryo, and have correlated the results with the ability of this factor to promote in vitro changes in the phenotype of mesoderm and epiblast cells. The findings, together with the demonstration that exogenous TGF beta 1 is also able to modulate extracellular matrix deposition by these cells in culture, are consistent with a role for this factor in the formation and morphogenesis of the early mesoderm. Immunofluorescence analysis, using an antibody to the amino-terminal fragment of TGF beta 1, indicates that this factor is located in, or between, cells of the medial epiblast, Hensen's node and primitive streak. At Hensen's node, cells of the hypoblast were also strongly labelled. Ingressed mesoderm cells, lateral to the streak, show considerably stronger and more diffuse labelling than the overlying epiblast cells. Although the fluorescent labelling appears to be associated with the extracellular matrix surrounding the mesoderm cells, it is not bound to hyaluronic acid, which is the preponderant molecule in the matrix at this time in development. When added exogenously to cultures of mesoderm cells growing with epithelial characteristics on fibronectin, TGF beta 1 effects an epithelial-mesenchymal transformation within 24 h. The reverse transformation is effected in mesoderm cells grown on laminin, while the epiblast cell phenotype is not affected by this treatment regardless of the substratum. TGF beta 1 is also able to down-regulate the deposition of fibronectin by mesoderm cells grown on fibronectin and of epiblast cells grown on laminin, but up-regulate fibronectin deposition by mesoderm on laminin. Similar substratum-dependent changes are seen in laminin deposition, which is down-regulated in mesoderm on laminin and up-regulated in epiblast on laminin. No effect on laminin deposition is seen in either cell type grown on fibronectin. Expression of the fibronectin receptor is also down-regulated by TGF beta 1 in mesoderm cells grown on fibronectin, and this may explain the decreased deposition of fibronectin associated with these cells under these conditions. We suggest that these results are consistent with a reinforcing role for TGF beta 1 in the transformation that results in the emergence of mesoderm cells at gastrulation. This factor may also be involved in the maintenance of the fibroblastic phenotype of the mesoderm cells after their ingression, by effects on the expression of receptors for extracellular matrix and on the deposition of matrix by these cells during their early morphogenesis.
Sanders
E J
EJ
Department of Physiology, University of Alberta, Edmonton, Canada.
Prasad
S
S
D000818:Animals; D002448:Cell Adhesion; D002642:Chick Embryo; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005775:Gastrula / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D005353:Fibronectins; D007797:Laminin; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta