Abstract

Moderate nutrient deprivation in animals is often compatible with development, albeit into an undersized adult. One important survival strategy here is to spare the growth of certain critical organs, such as the CNS , at the expense of others. For example, in humans, fetal nutrient restriction can result in asymmetric intrauterine growth restriction (IUGR), characterised by undersized neonates with relatively large brains. We have been exploring the molecular mechanisms underlying this type of brain sparing in the context of the growing CNS of Drosophila. This work has identified a highly modified Insulin/Tor signalling network that permits neural stem cells to grow and divide at the normal rate under conditions of nutrient restriction that are severe enough to shut down all net growth of the body. We also find that optimal CNS growth during this type of nutrient stress requires neural stem cells to be metabolically coupled to their glial-cell niche. The possible relevance of these findings to mammalian brain sparing and, more generally, to the mechanisms by which nutrients regulate the relative growth of different tissues will be discussed.

Selected Publications (last five years) Steinhauser, M.L, Bailey, A.P, Senyo, S.E, Guillermier, C, Perlstein, T.S, Gould, A.P, Lee, R.T and Lechene, C.P. (2012). Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism. Nature 481, 516-519 Cheng, L., Bailey, A., Leevers, S., Ragan, T., Driscoll, P. and Gould, A.P. (2011). Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila. Cell 146, 435-447. Sousa-Nunes, R, Yee, LL and Gould, A.P. (2011). Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature 471, 508-512. Maurange, C., Cheng, L., and Gould, A.P. (2008). Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell 133, 891-902. Miguel-Aliaga, I., Thor, S., and Gould, A.P. (2008). Postmitotic specification of Drosophila insulinergic neurons from pioneer neurons. PLoS Biology 6, e58. Gutierrez, E., Wiggins, D., Fielding, B. and Gould, A.P. (2007) Specialized hepatocyte-like cells regulate Drosophila lipid metabolism. Nature 445, 275-280.