Anteroposterior patterning and organogenesis of Xenopus laevis require a correct dose of germ cell nuclear factor (xGCNF).

The germ cell nuclear factor of Xenopus laevis (xGCNF; NR6A1) is a nuclear orphan receptor that is predominantly expressed during neurula and late tailbud stages. As a strategy to analyze the role of xGCNF in embryogenesis, we have induced a gain of function by overexpression of full-length (fl) GCNF and a functional inhibition by a dominant-negative (dn) GCNF. Early events of embryogenesis including gastrulation and neurulation were not affected and the expression of several early mesodermal markers was normal. Yet specific defects were observed upon organogenesis. Ectopic posterior overexpression of the full-length xGCNF caused posterior defects and disturbed somite formation. In contrast, expression of dnGCNF interfered with differentiation of the neural tube and affected the differentiation of anterior structures, including the cement gland and the eyes. Embryos affected by dnGCNF were rescued by coexpression of flGCNF. After expression of dnGCNF, mRNA encoding the the retinoic acid receptor xRAR gamma 2 was selectively suppressed anteriorly. From the distinct phenotypes obtained, we conclude that GCNF has an essential function in anteroposterior differentiation during organogenesis.