|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 121, Issue 12 4137-4148, Copyright © 1995 by Company of Biologists
JOURNAL ARTICLES |
O Behrendtsen, CM Alexander and Z Werb
Department of Anatomy and Program in Developmental Biology, University of California, San Francisco 94143-0750, USA.
The outgrowth of parietal endoderm (PE) cells from precursor endodermal cells is one of the first differentiation events that occur in mouse embryos. We have analyzed the molecular determinants of this process by placing isolated inner cell masses (ICMs) on defined extracellular matrix substrata in microdrop cultures. Differentiation and outgrowth of PE required a fibronectin substratum. Laminin supported the adhesion and outgrowth of visceral endoderm (VE) and actively suppressed the differentiation of PE in mixtures of fibronectin and laminin. Collagen type IV, gelatin, vitronectin or entactin supported little or no endodermal outgrowth. Trophectoderm (TE) cells have been implied to be important in PE induction in vivo. We found that recombination of ICMs in culture with TE cells, or with medium conditioned by TE cells, greatly increased the differentiation of PE. TE cells stimulated PE outgrowth on substrata other than fibronectin. One cytokine secreted by trophoblast and endodermal cells, parathyroid hormone-related peptide (PTHrP), was critical for outgrowth on any substratum. A function-perturbing antibody to PTHrP reduced the number of PE cells, whereas the addition of PTHrP increased that number. Furthermore, addition of PTHrP changed the substratum requirements for outgrowth, making laminin, vitronectin and low concentrations of fibronectin permissive for PE outgrowth. Immunostaining with anti-integrin antibodies showed that fully differentiated PE cells outgrowing on fibronectin expressed alpha 5, alpha 6 and alpha v beta 3 integrins. However, analysis of outgrowths in the presence of function-perturbing antibodies to alpha 5, alpha 6 and alpha v beta 3 integrins showed that these integrins directed PE outgrowth only on fibronectin, laminin and vitronectin substrata, respectively. We have shown that there is a cooperative interplay of extracellular matrix, integrins and PTHrP that modulates PE outgrowth.
This article has been cited by other articles:
|
|
 |
|
  A H K El-Hashash and S J Kimber Trophoblast differentiation in vitro: establishment and characterisation of a serum-free culture model for murine secondary trophoblast giant cells Reproduction, July 1, 2004; 128(1): 53 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Murray and D Edgar Regulation of the differentiation and behaviour of extra-embryonic endodermal cells by basement membranes J. Cell Sci., January 3, 2001; 114(5): 931 - 939. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Dunbar, P. Dann, G. Robinson, L Hennighausen, J. Zhang, and J. Wysolmerski Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development Development, January 8, 1999; 126(16): 3485 - 3493. [Abstract] [PDF]
|
|
|
|
 |
|
 R. A. Nowak, F. Haimovici, J. D. Biggers, and G. T. Erbach Transforming Growth Factor-ß Stimulates Mouse Blastocyst Outgrowth through a Mechanism Involving Parathyroid Hormone-Related Protein Biol Reprod, January 1, 1999; 60(1): 85 - 93. [Abstract] [Full Text]
|
|
|
|
 |
|
 V. Botquin, H. Hess, G. Fuhrmann, C. Anastassiadis, M. K. Gross, G. Vriend, and H. R. Schöler New POU dimer configuration mediates antagonistic control of an osteopontin preimplantation enhancer by Oct-4 and Sox-2 Genes & Dev., July 1, 1998; 12(13): 2073 - 2090. [Abstract] [Full Text]
|
|
