Remember That Gradient?

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Science  09 Dec 2005:
Vol. 310, Issue 5754, pp. 1589
DOI: 10.1126/science.310.5754.1589c

During early development, morphogen gradients instruct the differentiation of distinct cell types in proper spatial order. Exposure of cells to a specific concentration of morphogen can specify cell fate, but the exposure does not need to last for the several hours needed to complete execution of the gene expression program that drives the cell's response. Jullien and Gurdon explored how cells remember a brief exposure to morphogen by studying responses of Xenopus embryo cells to activin. Exposure for 10 min resulted in changes in gene expression several hours later. This response appeared to require continuous receptor signaling, because it could be inhibited at later stages by a pharmacological inhibitor of kinase activity of the activin receptor. Continued signaling also appeared to require receptor internalization, because a dominant-negative form of dynamin that prevents internalization of receptors from the plasma membrane inhibited activin-dependent gene expression when injected into embryonic cells. Expression of mutant Rab proteins that increase trafficking of membrane proteins through the lysosomal pathway (and thus increase the rate at which they are degraded) did not affect the memory of the activin signal, and the authors concluded that the signaling receptors have not yet entered the degradation pathway. Rather, it seems that the persistence of vesicles as they move from the plasma membrane to the lysosome accounts for the signal, and the authors propose that receptors activated by brief exposure to activin provide a prolonged signal. — LBR

enes Dev. 19, 2682 (2005).

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