Open Close
Poon, C.L., Mitchell, K.A., Kondo, S., Cheng, L.Y., Harvey, K.F. (2016). The Hippo Pathway Regulates Neuroblasts and Brain Size in Drosophila melanogaster.  Curr. Biol. 26(8): 1034--1042.
FlyBase ID
Publication Type
Research paper

A key question in developmental neurobiology is how neural stem cells regulate their proliferative potential and cellular diversity and thus specify the overall size of the brain. Drosophila melanogaster neural stem cells (neuroblasts) are known to regulate their ability to self-renew by asymmetric cell division and produce different types of neurons and glia through sequential expression of temporal transcription factors 1. Here, we show that the conserved Hippo pathway, a key regulator of epithelial organ size 2-4, restricts neuroblast proliferative potential and neuronal cell number to regulate brain size. The inhibition of Hippo pathway activity via depletion of the core kinases Tao-1, Hippo, or Warts regulates several key characteristics of neuroblasts during postembryonic neurogenesis. The Hippo pathway is required to maintain timely entry and exit from neurogenesis by regulating both neuroblast reactivation from quiescence and the time at which neuroblasts undergo terminal differentiation. Further, it restricts neuroblast cell-cycle speed, specifies cell size, and alters the proportion of neuron types generated during postembryonic neurogenesis. Collectively, deregulation of Hippo signaling in neuroblasts causes a substantial increase in overall brain size. We show that these effects are mediated via the key downstream transcription co-activator Yorkie and that, indeed, Yorkie overexpression in neuroblasts is sufficient to cause brain overgrowth. These studies reveal a novel mechanism that controls stem cell proliferative potential during postembryonic neurogenesis to regulate brain size.

PubMed ID
PubMed Central ID
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Curr. Biol.
    Current Biology
    Publication Year
    Data From Reference