mTOR kinase is needed for the development and stabilization of dendritic arbors in newly born olfactory bulb neurons

Abstract

Neurogenesis is the process of neuron generation, which occurs not only during embryonic development but also in restricted niches postnatally. One such region is called the subventricular zone (SVZ), which gives rise to new neurons in the olfactory bulb (OB). Neurons that are born postnatally migrate through more complex territories and integrate into fully functional circuits. Therefore, differences in the differentiation of embryonic and postnatally born neurons may exist. Dendritogenesis is an important process for the proper formation of future neuronal circuits. Dendritogenesis in embryonic neurons cultured in vitro was shown to depend on the mammalian target of rapamycin (mTOR). Still unknown, however, is whether mTOR could regulate the dendritic arbor morphology of SVZ‐derived postnatal OB neurons under physiological conditions in vivo. The present study used in vitro cultured and differentiated SVZ‐derived neural progenitors and found that both mTOR complex 1 and mTOR complex 2 were required for the dendritogenesis of SVZ‐derived neurons. Furthermore, using a combination of in vivo electroporation of neural stem cells in the SVZ and genetic and pharmacological inhibition of mTOR, it was found that mTOR was crucial for the growth of basal and apical dendrites in postnatally born OB neurons under physiological conditions and contributed to the stabilization of their basal dendrites. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1308–1327, 2016

mTOR signaling in stem and progenitor cells

“…In addition to regulating NSC differentiation, mTOR activity is required for dendrite formationa process that is essential for proper neuronal signaling (Skalecka et al, 2016). Treating rat embryonic neurons with mTOR inhibitors blocks the outgrowth of dendrites in vitro.…”

Dendrite and spine modifications in autism and related neurodevelopmental disorders in patients and animal models

“…Mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase that controls cell and organismal growth and is induced by growth factors and nutrients (Laplante and Sabatini, 2012). mTOR has been shown to play a role in shaping the actin cytoskeleton with a particular role in dendritogenesis (Kumar et al, 2005;Kim et al, 2009;Thomanetz et al, 2013;Skalecka et al, 2016). Proteins that repress mTOR have been linked to autism and also play a role in dendritic and spine morphology.…”

Low FoxO expression inDrosophilasomatosensory neurons protects dendrite growth under nutrient restriction

“…Dendrite growth in both insects and mammals is positively regulated by the conserved PI3K-Akt-mechanistic target of rapamycin (mTOR) pathway (Jaworski et al, 2005; Kumar et al, 2005; Parrish et al, 2009; Skalecka et al, 2016). Receiving signaling inputs from membrane receptor tyrosine kinases (RTKs), notably InR (Sancak et al, 2007; Vander Haar et al, 2007; Wang et al, 2007), this pathway enhances translation in most cells by mTOR kinase-mediated phosphorylation of S6 protein kinase (S6K) and 4E-binding protein (4E-BP) (Burnett et al, 1998).…”