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H V New

Publications and source records attributed to H V New.

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Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm.

The potent mesoderm-inducing factors activin and FGF are present as maternally synthesized proteins in embryos of X. laevis. We show that activin can act on explanted blastomeres to induce at least five different cell states ranging from posterolateral mesoderm to dorsoanterior organizer mesoderm. Each state is induced in a narrow dose range bounded by sharp thresholds. By contrast, FGF induces only posterolateral markers and does so over relatively broad dose ranges. FGF can modulate the actions of activin, potentiating them and broadening the threshold-bounded dose windows. Our results indicate that orthogonal gradients of activin and FGF would be sufficient to specify the main elements of the body plan.

Activins

Inductive interactions in early embryonic development.

This is an update of a previous review (Current Opinion in Cell Biology 2:969-974) in which we discussed recent work attempting to understand the sequence of inductive interactions responsible for establishing the body plan of the early embryo. As before, we concentrate on inductive interactions in amphibian embryos, where significant progress has been made in the past two years. In this update, however, we also consider recent embryological data obtained with amniote embryos such as the chick, together with complementary data provided by genetic analyses of mouse and Drosophila development.

Animals

Distribution and ontogeny of SP, CGRP, SOM, and VIP in chick sensory and sympathetic ganglia.

The distribution and ontogeny of four neuropeptides in developing chick lumbosacral sensory and sympathetic ganglia were studied using immunohistochemical techniques. Antibodies to two of these peptides, substance P (SP) and calcitonin gene-related peptide (CGRP), stained small neurons in the medial part of the dorsal root ganglia from embryonic Day 5 and Day 10, respectively, whereas neurons in the lateral part of the ganglia were negative; this distribution persisted throughout development. Both sets of neurons apparently send fibers to the dorsal horn of the spinal cord: SP to laminae I and II, and CGRP to lamina I, suggesting that the SP- and CGRP-positive sensory neurons are nociceptive or thermoreceptive. This correlation between the presence of SP or CGRP in a neuron and a particular functional modality thus provides evidence for a functional distinction between the mediodorsal and ventrolateral zones that are apparent during the development of chick dorsal root ganglia. Moreover, this study suggests that the type of neuron that develops within the dorsal root ganglion correlates with its position within the ganglion. In contrast to SP and CGRP, somatostatin (SOM) and vasoactive intestinal polypeptide (VIP) immunoreactivities were not seen in the lumbosacral sensory ganglia at any stage during development. However, both were present in sympathetic ganglia: SOM from embryonic Day 4.5 and VIP from embryonic Day 10. VIP immunoreactivity persisted throughout development in a large number of sympathetic neurons, but the number of cells with SOM immunoreactivity decreased from embryonic Day 10 onward. SOM therefore appears to be present only transiently in most chick lumbosacral sympathetic cells.

Animals

Calcitonin gene-related peptide regulates muscle acetylcholine receptor synthesis.

Innervation of muscle by motoneurones induces the development of a characteristic, high density cluster of acetylcholine receptors (AChRs) at the neuromuscular junction. Studies in vitro show that the accumulation of AChRs at nerve-muscle contacts results from both increased insertion of new AChRs into the muscle plasma membrane beneath nerve terminals and redistribution of preexisting AChRs; these two modes of AChR accumulation may be separately controlled since factors have been identified that influence AChR redistribution but not synthesis. Although many aspects of muscle development are regulated by nerve-dependent muscle activity, junctional AChR clusters still develop when neuromuscular transmission is blocked by either curare or alpha-bungarotoxin, suggesting that their formation is mediated by nerve-derived trophic factors other than activity. A molecule immunologically related to calcitonin gene-related peptide (CGRP-I) has been found in motoneurones in a variety of mammals including man. Here we provide indirect evidence that CGRP-I may be a motoneurone-derived trophic factor that increases AChR synthesis at vertebrate neuromuscular junctions.

Acetylcholinesterase