July 14, 2008 In the July 15th issue of Genes & Development, Dr. Matthew Scott and colleagues at Stanford University School of Medicine reveal that a protein called Nucleostemin 3 links the serotonin and insulin signaling pathways in the control of Drosophila body size.
Nucleostemin proteins were originally identified in mammals, where they are associated with undifferentiated, proliferating stem cells. In human cells, Nucleostemin expression has been linked with certain types of cancer.
Initial work in the Scott lab into the developmental roles of Drosophila Nucleostemin proteins led the researchers towards a focus on the specific role of Nucleostemin 3 (NS3) in the regulation of growth and body size. The researchers found that NS3-deficient flies are about 60% smaller than normal, displaying both a reduced cell size and number, but having otherwise normal body proportions -- a phenotype traditionally associated with defective insulin signaling.
Cell-specific NS3 disruption revealed that, although NS3 is expressed in several different cell types, it is required only in 106 serotonin-producing neurons to affect the overall organismal body size. Furthermore, the growth defect can be rescued by the introduction of NS3 expression into these serotonergic neurons.
Dr. Scott and colleagues demonstrated that within the fly brain, serotonergic neurons are situated in close proximity to insulin-producing cells, and thus suggest that NS3 functions in serotonergic neurons to influence insulin signaling and thereby regulate body size.
Dan Kaplan, a Stanford postdoctoral fellow working with Professors Scott and Tobias Meyer, is the first author of the study. He comments that "serotonin and insulin/insulin-like growth factor signaling mechanisms are evolutionarily conserved between flies and humans. We hope that our work in the fly will lead to new insights about the control of these pathways in humans, which could help us to understand, for example, how insulin signaling is mis-regulated in diabetes, or how insulin-like growth factor pathways are perturbed in developmental growth disorders or cancers."
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