Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain

Science. 2014 May 30;344(6187):1020-3. doi: 10.1126/science.1252514. Epub 2014 May 15.


Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Brain / growth & development*
  • Brain / metabolism
  • Gene Knockdown Techniques
  • Mice
  • Mice, Inbred C57BL
  • Purkinje Cells / metabolism
  • Purkinje Cells / physiology*
  • RNA Interference
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / metabolism
  • Semaphorin-3A / genetics
  • Semaphorin-3A / metabolism*
  • Semaphorins / genetics
  • Semaphorins / metabolism*
  • Signal Transduction
  • Synapses / genetics
  • Synapses / physiology*


  • Antigens, CD
  • Receptors, Metabotropic Glutamate
  • Sema3a protein, mouse
  • Sema7a protein, mouse
  • Semaphorin-3A
  • Semaphorins
  • metabotropic glutamate receptor type 1