Knowing How to Navigate: Mechanisms of Semaphorin Signaling in the Nervous System

Sci. STKE, 12 February 2002
Vol. 2002, Issue 119, p. re1
DOI: 10.1126/stke.2002.119.re1

Knowing How to Navigate: Mechanisms of Semaphorin Signaling in the Nervous System

  1. Zhigang He1,*,
  2. Kevin C. Wang1,
  3. Vuk Koprivica1,
  4. Guoli Ming2, and
  5. Hong-Jun Song3
  1. 1Division of Neuroscience, Children's Hospital, and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
  2. 2Department of Biology, University of California at San Diego, La Jolla, CA 92093, USA.
  3. 3Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  1. *Corresponding author. E-mail: zhigang.he{at}


Neuronal connections are made during embryonic development with astonishing precision to ultimately form the physical basis for the central nervous system's main capacity: information processing. Over the past few decades, much has been learned about the general principles of axon guidance. A key finding to emerge is that extracellular cues play decisive roles in establishing the connections. One family of such cues, the semaphorin proteins, was first identified as repellents for navigating axons during brain wiring. Recent studies have implicated these molecules in many other processes of neuronal development, including axonal fasciculation, target selection, neuronal migration, and dendritic guidance, as well as in the remodeling and repair of the adult nervous system. It appears that responding neuronal processes sense these semaphorin signals by a family of transmembrane molecules, namely the plexins, even though neuropilins were also found to be required for mediating the interaction between plexins and class 3 semaphorins. Our understanding of the intracellular signaling machinery linking the receptors to the cytoskeleton machinery is still incomplete, but several molecules have been implicated in mediating or modulating semaphorin-induced responses. Adding to the complexity of semaphorin biology, new findings implicate semaphorins in functioning not only as signaling ligands, but also as signal-transducing receptors. Thus, semaphorins may serve as important probes for exploring the mechanisms of intercellular communication during the development and function of the nervous system.


Z. He, K. C. Wang, V. Koprivica, G. Ming, and H.-J. Song, Knowing How to Navigate: Mechanisms of Semaphorin Signaling in the Nervous System. Sci. STKE 2002, re1 (2002).

Differential regulation of actin microfilaments by human MICAL proteins
S. S. P. Giridharan, J. L. Rohn, N. Naslavsky, and S. Caplan
J. Cell Sci. 125, 614-624 (1 February 2012)

Type III neuregulin 1 regulates pathfinding of sensory axons in the developing spinal cord and periphery
M. L. Hancock, D. W. Nowakowski, L. W. Role, D. A. Talmage, and J. G. Flanagan
Development 138, 4887-4898 (15 November 2011)

Maturation of the olfactory sensory neurons by Apaf-1/caspase-9-mediated caspase activity
S. Ohsawa, S. Hamada, K. Kuida, H. Yoshida, T. Igaki, and M. Miura
Proc. Natl. Acad. Sci. USA 107, 13366-13371 (27 July 2010)

Class 3 Semaphorin Signaling: The End of a Dogma
V. Potiron, and J. Roche
Sci Signal 2005, pe24-pe24 (24 May 2005)

Semaphorin 3E and Plexin-D1 Control Vascular Pattern Independently of Neuropilins
C. Gu, Y. Yoshida, J. Livet, D. V. Reimert, F. Mann, J. Merte, C. E. Henderson, T. M. Jessell, A. L. Kolodkin, D. D. Ginty et al.
Science 307, 265-268 (14 January 2005)

CB1 Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity
G. Marsicano, S. Goodenough, K. Monory, H. Hermann, M. Eder, A. Cannich, S. C. Azad, M. G. Cascio, S. O. Gutierrez, M. van der Stelt et al.
Science 302, 84-88 (3 October 2003)

Signaling Receptome: A Genomic and Evolutionary Perspective of Plasma Membrane Receptors Involved in Signal Transduction
I. Ben-Shlomo, S. Yu Hsu, R. Rauch, H. W. Kowalski, and A. J. W. Hsueh
Sci Signal 2003, re9-re9 (17 June 2003)

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882