The first inductive interaction in amphibian development is mesoderm induction, when a signal from the vegetal hemisphere of the blastula induces mesoderm from overlying equatorial cells. Recently, several 'mesoderm-inducing factors' (MIFs) have been discovered. These cause isolated Xenopus animal caps to form mesodermal cell types such as muscle, instead of their normal fate of epidermis. The MIFs fall into two classes. One comprises members of the fibroblast growth factor (FGF) family, and the other members of the transforming growth factor type beta (TGF-beta) family. Of the latter group, the most potent is XTC-MIF, a protein produced by Xenopus XTC cells. Here we show that XTC-MIF is the homologue of mammalian activin A. Activins modulate the release of follicle-stimulating hormone from cultured anterior pituitary cells and cause the differentiation of two erythroleukaemia cell lines. Our results indicate that these molecules may also act in early development during formation of the mesoderm.

Bone morphogenetic proteins (BMPs) and their receptors, known to be essential regulators of embryonal patterning and organogenesis, are also critical for the regulation of cardiovascular structure and function. In addition to their contributions to syndromic disorders of heart and vascular development, BMP signalling is increasingly recognized for its influence on endocrine-like functions in postnatal cardiovascular and metabolic homeostasis. In this Review, we discuss several critical and novel aspects of BMP signalling in cardiovascular health and disease, which highlight the cell- and context-specific nature of BMP signalling. Based on advancing knowledge of the physiological roles and regulation of BMP signaling, we indicate opportunities for therapeutic intervention in a range of cardiovascular conditions including atherosclerosis and pulmonary arterial hypertension, and well as for anaemia of chronic disease. Depending on the context and the repertoire of ligands and receptors involved in specific disease processes, the selective inhibition or enhancement of signaling via particular BMP ligands (such as in atherosclerosis and pulmonary arterial hypertension, respectively) might be beneficial. The development of selective small molecule antagonists of BMP receptors, and the identification of ligands selective for BMP receptor complexes expressed in the vasculature provide the most immediate opportunities for new therapies.

Using a 1.5-tesla GE Signa MR scanner, we imaged the brains of 14 right-handed Tourette's syndrome (TS) patients (11 men, three women), aged 18 to 49 years, who had minimal lifetime neuroleptic exposure. We also studied an equal number of normal controls individually matched for age, sex, and handedness and group-matched for socioeconomic status. We circumscribed basal ganglia on sequential axial images from spin-echo proton density-weighted acquisitions (TR 1,700, TE 20; slice thickness, 3 mm with 1.5-mm skip) and submitted the images for three-dimensional processing at a computer graphics workstation. Our hypothesis of lenticular nucleus volume reduction in TS was confirmed for the left- but not the right-sided nucleus. Post hoc analyses revealed smaller mean volumes of the caudate, lenticular, and globus pallidus nuclei compared with controls on both the right and left. Further analyses of basal ganglia asymmetry indices suggest that TS basal ganglia do not have the volumetric asymmetry (left greater than right) seen in normal controls. These findings confirm and extend prior phenomenologic, neuropathologic, and neuroradiologic studies that implicate the basal ganglia in the pathogenesis of TS.

The protein XTC-MIF, a Xenopus homologue of activin A and a potent mesoderm-inducing factor, can induce responding animal pole explants to form several different cell types in a dose-dependent manner, higher doses eliciting more dorso-anterior tissues. This graded response, characteristic of classically postulated morphogens, may underlie pattern formation, but the response of intact animal caps to XTC-MIF provides only a crude indication of trends. Here we report the effects of XTC-MIF on dispersed blastomeres rather than intact animal caps. Under these conditions, responding cells distinguish sharply between doses of pure XTC-MIF differing by less than 1.5-fold. Two different response thresholds have been found, defining three cell states. This suggests that XTC-MIF has an instructive effect. Notochord and muscle are both induced in the same narrow dose-range. Mixing treated with untreated cells does not seem to shift the dose thresholds, showing that at least some cells can stably record the received dose of inducing factor.

Recent advances in avian transgenesis have led to the possibility of utilizing the laying hen as a production platform for the large-scale synthesis of pharmaceutical proteins. Ovalbumin constitutes more than half of the protein in the white of a laid egg, and expression of the ovalbumin gene is restricted to the tubular gland cells of the oviduct. Here we describe the use of lentiviral vectors to deliver transgene constructs comprising regulatory sequences from the ovalbumin gene designed to direct synthesis of associated therapeutic proteins to the oviduct. We report the generation of transgenic hens that synthesize functional recombinant pharmaceutical protein in a tightly regulated tissue-specific manner, without any evidence of transgene silencing after germ-line transmission.chicken ͉ genetic modification ͉ lentivirus ͉ pharmaceutical