Spare the Brain

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Science  19 Aug 2011:
Vol. 333, Issue 6045, pp. 920
DOI: 10.1126/science.333.6045.920-b
CREDIT: CHENG ET AL., CELL 146, 435 (2011)

During development, periods of nutrient deprivation can shut down body tissue and organ growth as a survival strategy, but somehow the brain is protected and continues to mature. This phenomenon occurs in many animals, from flies to humans, but little has been known about how the central nervous system gains this growth advantage. Cheng et al. report that in the model organism Drosophila melanogaster, nutrient withdrawal blocks late larval-stage body growth, but brain neural stem cells (neuroblasts) continue to grow and divide at a normal rate. This neural sparing requires a tyrosine kinase receptor called anaplastic lymphoma kinase (ALK). ALK activity during nutrient deprivation specifically suppressed the reliance of neuroblasts on the insulin receptor (which controls the cellular growth response to insulin-like peptides) and TOR (a component of a signaling pathway that senses amino acids) to survive. Disabling these pathways did not affect growth of the brain, yet growth was blunted in other larval tissues. ALK promotes neural growth by somehow activating downstream targets of the insulin receptor and TOR. The authors also determined that secretion of Jelly belly—the activating ligand for ALK—by glia does not depend on nutrient availability either. Besides providing insight into neural growth during nutrient deprivation, the fact that ALK regulates two growth-controlling signaling pathways may explain why ALK mutations are associated with human cancers, including neuroblastoma.

Cell 146, 435 (2011).

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