Carboxypeptidase Z (CPZ) is a secreted Zn-dependent enzyme whose biological function is largely unknown. CPZ has a bipartite structure consisting of an N-terminal cysteine-rich domain (CRD) and a C-terminal catalytic domain. In the early chicken embryo CPZ is initially expressed throughout the somites and subsequently becomes restricted to the sclerotome. To initiate a functional analysis of CPZ, a CPZ producing retroviral vector was applied to the presomitic mesoderm at the level of the future wing. This resulted in a loss of the scapular blade and of rostral ribs. Such dysmorphogenesis is preceded by ectopic Pax3 expression in the hypaxial part of the dermomyotome,a region from which the blade of the scapula normally derives. A mutant CPZ,lacking a critical active site glutamate, fails to induce Pax3expression and does not cause skeletal defects. The induction of Pax3, a Wnt-responsive gene in somites, and the presence of a CRD prompted us to examine whether CPZ affects Wnt signaling. In an in vitro assay we found that CPZ, but not its inactive mutant form, enhances the Wnt-dependent induction of the homeobox gene Cdx1. In addition,immunoprecipitation experiments suggest that the CRD of CPZ acts as a binding domain for Wnt. Taken together these data provide the first evidence for CPZ playing a role in Wnt signaling.

The studies took place at Bayer Pharma AG. All authors are employees of Bayer Pharma AG. No external funding declared.

Limb Expression 1 (Lix1), a founding member of a novel gene family, was identified in a screen for genes transiently and locally expressed during early chicken limb development. Most prominently, Lix1 is transiently expressed in the nascent hindlimb bud between Hamburger-Hamilton stages 15 and 19. Chicken Lix1 transcripts are also found in the basal plate of rhombomeres 3 and 5, in pharyngeal and in foregut mesenchyme and in all facial primordia except for the mandibular arches. Homologs of chick Lix1 exist in human, mouse and Drosophila.

We describe the expression of Lix1 in the mouse. Starting at E8, transcripts are present in a regionalized fashion and persist throughout development. mLix1 is expressed in the cortical plate, subventricular zone, layer 5 of the postnatal cortex, the substantia nigra, dorsal root ganglia, specific nuclei of the brain stem and in spinal cord. Limb buds and facial primordia show transient expression. The prominent expression of mLix1 in the developing cerebral cortex and in the substantia nigra pars compacta makes this novel gene a candidate marker for both of these tissues.

Purpose: Evidence from real-world settings is important to provide an accurate picture of health care delivery. We investigated use of long-acting reversible contraception (LARC) in women aged 15-49 years. Materials and methods: Two surveys, one of women and one of health care professionals (HCPs), were conducted in parallel across seven countries. Participating women completed an online survey to assess contraceptive awareness, current method of contraception, age, and experience with current contraceptive method. HCPs participated in an online survey to provide practice-level information and three anonymous charts of hormonal LARC users. Results: Of 6903 women who completed the survey, 3225 provided information about their current primary contraception method. Overall, 16% used LARC methods, while 52% used oral contraceptives (OCs). Of hormonal intrauterine system users, 72% described their experience as 'very favourable', compared with only 53% of women using OCs. Anonymous patient records (n ¼ 1605) were provided by 550 HCPs who completed the online survey. Most women (64%) had used short-acting reversible contraception before switching to LARC. Physicians perceived 56-84% of LARC users to be highly satisfied with their current form of contraception. Conclusions: Although usage of LARC was low, most women using LARC were highly satisfied with their method of contraception.