Self-amplifying autocrine actions of BDNF in axon development

Pei Lin Cheng, Ai Hong Song, Yu Hui Wong, Sheng Wang, Xiang Zhang, Mu Ming Poo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

183 Scopus citations


A critical step in neuronal development is the formation of axon/ dendrite polarity, a process involving symmetry breaking in the newborn neuron. Local self-amplifying processes could enhance and stabilize the initial asymmetry in the distribution of axon/dendrite determinants, but the identity of these processes remains elusive. We here report that BDNF, a secreted neurotrophin essential for the survival and differentiation ofmany neuronal populations, serves as a self-amplifying autocrine factor in promoting axon formation in embryonic hippocampal neurons by triggering two nested positive-feedback mechanisms. First, BDNF elevates cytoplasmic cAMP and protein kinase A activity, which triggers further secretion of BDNF and membrane insertion of its receptor TrkB. Second, BDNF/TrkB signaling activates PI3-kinase that promotes anterograde transport of TrkB in the putative axon, further enhancing local BDNF/TrkB signaling. Together, these self-amplifying BDNF actions ensure stable elevation of local cAMP/protein kinase A activity that is critical for axon differentiation and growth.

Original languageEnglish
Pages (from-to)18430-18435
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
StatePublished - 8 Nov 2011


  • Axon initiation and growth
  • cAMP/protein kinase A elevation
  • Neurotrophin autocrine loops
  • Trk redistribution


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