AUTONOMOUS ENDODERMAL DETERMINATION IN XENOPUS - REGULATION OF EXPRESSION OF THE PANCREATIC GENE X1HBOX-8

In neural plate stage Xenopus embryos, X1Hbox 8 expression marks anter ior endodermal cells fated to develop into pancreas/duodenum, and expr ession continues in adult pancreas in exocrine duct, acinar, and islet cells. Here, X1Hbox 8 is used as a marker in experiments addressing t he mechanisms of early endodermal patterning, particularly with respec t to the role of specific polypeptide growth factors. When mesoderm-fr ee vegetal explants (VEs) from early blastula stage embryos are cultur ed in isolation, X1Hbox 8 expression develops autonomously in the dors al region, strongly suggesting that endodermal region-specific determi nation occurs before MBT. Data from microinjection experiments using R NA encoding the activin and FGF dominant negative receptors and growth factor treatments of isolated VEs suggest that activin positively reg ulates X1Hbox 8 expression, whereas bFGF is a potent negative regulato r. Moreover, bFGF induces mesodermal marker expression in VEs. This su ggests that the early endodermal determination state is plastic and th at elevated levels of bFGF may convert vegetal (endodermal) cells into mesoderm. We propose a model for X1Hbox 8 regulation in which an earl y signal from the Nieuwkoop center (whose eventual fate is endoderm) p redisposes dorsovegetal cells for autonomous X1Hbox 8 expression, in a n area of high local activin (or activin-like) ligand concentration, a nd low relative concentrations of bFGF. (C) 1995 Academic Press, Inc.