SEQUENTIAL EXPRESSION OF HNF-3-BETA AND HNF-3-ALPHA BY EMBRYONIC ORGANIZING CENTERS - THE DORSAL LIP NODE, NOTOCHORD AND FLOOR PLATE/

Axial patterning in the nervous system of vertebrate embryos depends o n inductive signals that derive from the organizer region (the dorsal lip in amphibians and the node in birds and mammals) and later from th e notochord and floor plate. Previous studies have shown that Pintalla vis, a member of the HNF-3/fork head transcription factor family, is e xpressed selectively by these cell groups in frog embryos and may be i nvolved in regulating neural development. We report here that in early rat and mouse embryos, the embryonic endoderm, the node, the notochor d and the floor plate express two related transcription factors, HNF-3 alpha and HNF-3 beta, which also function in the control of liver cel l differentiation. Early embryonic tissues express variant forms of HN F-3 beta which derive from the use of 5' alternative exons. Within the organizer region and notochord, HNF-3 beta and HNF-3 alpha have disti nct temporal patterns of expression and appear in partially overlappin g domains. The early expression pattern of mammalian HNF-3 beta in the node, notochord and midline neural plate cells is similar to that of Pintallavis in frog embryos. There does not appear to be a Pintallavis homologue in mice. This prompted us to isolate and analyze the expres sion of the frog HNF-3 beta gene. In frog embryos, HNF-3 beta is expre ssed in the dorsal lip, pharyngeal endoderm and floor plate. In contra st to mammalian HNF-3 beta, the onset of frog HNF-3 beta expression in neural tissue occurs after neural tube closure. Thus, the combined ex pression patterns of Pintallavis and HNF-3 beta in frogs is equivalent to that of HNF-3 beta in rats and mice. Within neural tissue, the ons et of expression of these regulatory genes define successive stages in the differentiation of floor plate cells. The results reported here s how that closely related members of the HNF-3/fork head gene family ar e expressed by axial midline cell groups involved in neural induction and patterning and suggest the involvement of these genes in the devel opment of the vertebrate neuraxis.