MRC National Institute for Medical Research, London
Science for Health
Signals from fat tissue stimulate nervous system growth
23 February 2011
NIMR scientists have used an integrative physiology approach in fruit flies to identify a tissue-to-tissue relay mechanism controlling the growth and proliferation of neural progenitors. The research is published in Nature.
Many stem, progenitor and cancer cells undergo periods of mitotic quiescence from which they can be reactivated. However, the signals triggering exit from this quiescent state are not well understood. In the developing Drosophila central nervous system (CNS), multipotent self-renewing progenitors called neuroblasts exit quiescence (reactivate) in response to dietary nutrients.
Rita Sousa-Nunes and Alex Gould (pictured below) from NIMR’s Division of Developmental Neurobiology, used tissue-specific genetic manipulations in fruit flies to identify the molecular mechanism by which neuroblast reactivation is regulated by dietary nutrients. The concentration of amino acids in the blood (hemolymph) of the larva is sensed by adipose tissue and, if sufficiently high, triggers this tissue to release a systemic signal into the blood. Within the CNS, glial cells then respond to the signal by secreting Insulin-like peptides. In turn, Insulin-like peptides trigger the entry of neuroblasts into the cell cycle. In this way, adipose tissue is able to sense whether there are enough nutrients available to commit to the energy-intensive programme of building an adult brain.
Rita Sousa-Nunes and Alex Gould
These new findings indicate that it will be worthwhile investigating whether human adipose tissue sends similar signals to glial cells. The available evidence already points to at least some degree of evolutionary conservation in the relay mechanism as Insulin-like growth factor is known to stimulate mammalian neural progenitors to divide.
It is well established that local tissue environments called niches regulate the proliferation of neural stem cells and progenitors in the growing brain. Our Drosophila study now highlights that global circulating signals and dietary nutrients are also important for this process. Without wishing to overspeculate, it seems important from a stem cell therapy perspective to find out how environmental factors such as the patient's diet may affect the behaviour of implanted stem cells and thus the efficacy of treatments
Alex Gould
Tissue-to-tissue relay model for amino-acid regulation of Drosophila growth
Click image to view at full-size
High amino-acid concentrations stimulate adipose tissue (fat body) to release a signal (FDS) that regulates the production of Insulin-like peptides (Ilps) from glia and also from specialized medial neurosecretory cells (mNSCs). Glial-derived Ilps (green) trigger the proliferation of neuroblasts (red) and thus the growth of the CNS. In contrast, mNSC-derived Ilps (purple) systemically regulate the growth of other larval tissues.
Original article
Rita Sousa-Nunes, Lih Ling Yee and Alex P. Gould (2011)
Fat cells reactivate quiescent neuroblasts via TOR and glial Insulin relays in Drosophila
Nature, Epub ahead of print. Publisher abstract
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