The defective gene responsible for Duchenne muscular dystrophy in humans and the dystrophic condition in mdx mice results in a lack of dystrophin at first thought to be localized to the triads, but more recently found on the cytoplasmic side of the sarcolemma of skeletal muscle fibres. Because the total calcium content of dystrophic fibres is significantly raised, we have compared the intracellular free calcium concentration [( Ca2+]i) in skeletal muscle in normal and mdx mice. We find that [Ca2+]i is markedly elevated in mdx muscle fibres compared with normal fibres, both at rest and during stimulation. By measuring protein degradation rates and manipulating [Ca2+]i, we have been able to demonstrate directly that the elevation of [Ca2+]i in mdx fibres results in an enhanced net degradation of muscle proteins.

Abstract. Motile chick skeletal fibroblasts adhere to a laminin substrate by means of clustered/3~ integrins. These integfin "macroaggregates" are similar to classic focal contacts but do not appear dark under interference-reflection microscopy. They contain ~5 integrin and are associated with extracellular fibronectin. To study their behavior during cell movement, time-lapse, low-light video microscopy was used to image integrins on living cells tagged with a fluorescent anti-#~ integrin antibody.Integrin macroaggregates remain fixed with respect to the substratum, despite the fact that they fluctuate in size, density, and shape over a period of minutes. Upon detachment of the cell rear, as much as 85 % of the ~ integrin density of a macroaggregate remains behind on the substrate, along with both or5 integrin and fibronectin. Release of the cell rear does not involve cleavage of the ~ integrin cytoplasmic domain from the remainder of the protein. These resuits indicate that cell motility does not require regulated detachment of integrin receptors from the substrate. On the other hand, cytoskeletal components and a variable fraction of the integrins are carried forward with the cell during detachment, suggesting that some type of cortical disassembly process does Occur.

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The discovery that lithium treatment at blastula stages can induce axis formation suggested that it might act by respecifying the cytoplasmic rearrangement-generated dorsoventral pattern, so that ventral cells behave like their dorsal counterparts. We have studied the effects of Li+ treatment on the spatial layout of the cell-group movements of gastrulation to see whether this is the case. We find that involution of the chordamesoderm and associated archenteron roof is retarded by Li+, an effect which does not suggest dorsal respecification. However, in both migration of the leading edge mesoderm and convergent extension of the marginal zone, ventral regions clearly do show dorsal-type movement. Because of this, and because of examples where disruption of involution and effects on axis differentiation do not correlate, we propose that failure of involution represents a distinct effect of Li+ involving disruption of mechanical relationships at the blastopore. Thus archenteron formation poorly reflects the dorsoventral pattern. Extension of sandwich explants of the ventral marginal zone is proposed as a reliable quantitative assay for alterations to the dorsoventral pattern.