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The developmental mechanisms by which growth is coordinated among developing organs are largely unknown and yet are essential to generate a correctly proportioned adult. In particular, such coordinating mechanisms must be able to accommodate perturbations in the growth of individual organs caused by environmental or developmental stress. By autonomously slowing the growth of the developing wing discs within Drosophila larvae, we show that growing organs are able to signal localized growth perturbation to the other organs in the body and slow their growth also. Growth rate is so tightly coordinated among organs that they all show approximately the same reduction in growth rate as the developing wings, thereby maintaining their correct size relationship relative to one another throughout development. Further, we show that the systemic growth effects of localized growth-perturbation are mediated by ecdysone. Application of ecdysone to larvae with growth-perturbed wing discs rescues the growth rate of other organs in the body, indicating that ecdysone is limiting for their growth, and disrupts the coordination of their growth with growth of the wing discs. Collectively our data demonstrate the existence of a novel growth-coordinating mechanism in Drosophila that synchronizes growth among organs in response to localized growth perturbation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

To evaluate the importance of altered pyrimidine synthesis in the relationship between immune dysfunction and deficiency of ADA, this pathway has been evaluated in normal and ADA-deficient human lymphoblasts. Adenosine and deoxyadenosine effect comparable reductions of radiolabeled bicarbonate incorporation in uridine nucleosides of both normal and deficient cells, with this effect being more prolonged in deficient cells. In ADA-deficient lymphoblasts this altered pyrimidine metabolism is accompanied by reduced intracellular concentrations of PP-ribose-P with adenosine but not deoxyadenosine. The altered PP-ribose-P levels are accompanied by orotic acid accumulation, but this block does not fully account for the net reduction in uridine nucleotide synthesis. This suggests interference of the pyrimidine pathway at another locus, possibly by altered carbamyl phosphate synthetase activity. The mechanism for deoxyadenosine-mediated inhibition is obscure. Despite the demonstrable adenosine- and deoxyadenosine-mediated alterations of pyrimidine metabolism, these changes are not accompanied by marked interference of cell growth for both normal and ADA-deficient lymphoblasts. These data support the hypothesis that altered pyrimidine metabolism is not the basis for the immune disorder in patients with deficiency of ADA.