Mice lacking the orphan receptor ror1 have distinct skeletal abnormalities and are growth retarded.

Ror1 is a member of the Ror-family receptor tyrosine kinases. Ror1 is broadly expressed in various tissues and organs during mouse embryonic development. However, so far little is known about its function. The closely related family member Ror2 was shown to play a crucial role in skeletogenesis and has been shown to act as a co-receptor for Wnt5a mediating non-canonical Wnt-signaling. Previously, it has been shown that during embryonic development Ror1 acts in part redundantly with Ror2 in the skeletal and cardiovascular systems. In this study, we report that loss of the orphan receptor Ror1 results in a variety of phenotypic defects within the skeletal and urogenital systems and that Ror1 mutant mice display a postnatal growth retardation phenotype.

Differential requirement for the dual functions of ß-catenin in embryonic stem cell self-renewal and germ layer formation.

Canonical Wnt signalling has been implicated in mouse and human embryonic stem cell (ESC) maintenance; however, its requirement is controversial. ß-catenin is the key component in this highly conserved Wnt pathway, acting as a transcriptional transactivator. However, ß-catenin has additional roles at the plasma membrane regulating cell-cell adhesion, complicating the analyses of cells/tissues lacking ß-catenin. We report here the generation of a Ctnnb1 (ß-catenin)-deficient mouse ESC (mESC) line and show that self-renewal is maintained in the absence of ß-catenin. Cell adhesion is partially rescued by plakoglobin upregulation, but fails to be maintained during differentiation. When differentiated as aggregates, wild-type mESCs form descendants of all three germ layers, whereas mesendodermal germ layer formation and neuronal differentiation are defective in Ctnnb1-deficient mESCs. A Tcf/Lef-signalling-defective ß-catenin variant, which re-establishes cadherin-mediated cell adhesion, rescues definitive endoderm and neuroepithelial formation, indicating that the ß-catenin cell-adhesion function is more important than its signalling function for these processes.