TY - JOUR
T1 - TGF-β Signaling Specifies Axons during Brain Development
AU - Yi, Jason J.
AU - Barnes, Anthony P.
AU - Hand, Randal
AU - Polleux, Franck
AU - Ehlers, Michael D.
N1 - Funding Information:
We thank Irina Lebedeva and Marguerita Klein for excellent technical assistance and Ben Arenkiel, Ian Davison, Juliet Hernandez, Matt Kennedy, and Fan Wang for helpful discussion and critical review of the manuscript. We thank Irwin Liu and Xiao-Fan Wang for the Tgfbr1 shRNA constructs. This work was supported by grants from the NIMH and NINDS to M.D.E. and a Ruth K. Broad Biomedical Foundation fellowship to J.J.Y. M.D.E. is an Investigator of the Howard Hughes Medical Institute.
PY - 2010/7
Y1 - 2010/7
N2 - In the mammalian brain, the specification of a single axon and multiple dendrites occurs early in the differentiation of most neuron types. Numerous intracellular signaling events for axon specification have been described in detail. However, the identity of the extracellular factor(s) that initiate neuronal polarity in vivo is unknown. Here, we report that transforming growth factor β (TGF-β) initiates signaling pathways both in vivo and in vitro to fate naive neurites into axons. Neocortical neurons lacking the type II TGF-β receptor (TβR2) fail to initiate axons during development. Exogenous TGF-β is sufficient to direct the rapid growth and differentiation of an axon, and genetic enhancement of receptor activity promotes the formation of multiple axons. Finally, we show that the bulk of these TGF-β-dependent events are mediated by site-specific phosphorylation of Par6. These results define an extrinsic cue for neuronal polarity in vivo that patterns neural circuits in the developing brain.
AB - In the mammalian brain, the specification of a single axon and multiple dendrites occurs early in the differentiation of most neuron types. Numerous intracellular signaling events for axon specification have been described in detail. However, the identity of the extracellular factor(s) that initiate neuronal polarity in vivo is unknown. Here, we report that transforming growth factor β (TGF-β) initiates signaling pathways both in vivo and in vitro to fate naive neurites into axons. Neocortical neurons lacking the type II TGF-β receptor (TβR2) fail to initiate axons during development. Exogenous TGF-β is sufficient to direct the rapid growth and differentiation of an axon, and genetic enhancement of receptor activity promotes the formation of multiple axons. Finally, we show that the bulk of these TGF-β-dependent events are mediated by site-specific phosphorylation of Par6. These results define an extrinsic cue for neuronal polarity in vivo that patterns neural circuits in the developing brain.
KW - Molneuro
UR - http://www.scopus.com/inward/record.url?scp=77954256913&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2010.06.010
DO - 10.1016/j.cell.2010.06.010
M3 - Article
C2 - 20603020
AN - SCOPUS:77954256913
SN - 0092-8674
VL - 142
SP - 144
EP - 157
JO - Cell
JF - Cell
IS - 1
ER -