Neurotrophin receptors TrkA and TrkC cause neuronal death whereasTrkB does not

Vassiliki Nikoletopoulou, Heiko Lickert, José Maria Frade, Chantal Rencurel, Patrizia Giallonardo, Lixin Zhang, Miriam Bibel, Yves Alain Barde

Research output: Contribution to journalArticlepeer-review

176 Scopus citations

Abstract

Neurons of the peripheral nervous system have long been known to require survival factors to prevent their death during development. But why they selectively become dependent on secretory molecules has remained a mystery, as is the observation that in the central nervous system, most neurons do not show this dependency. Using engineered embryonic stem cells, we show here that the neurotrophin receptors TrkA and TrkC (tropomyosin receptor kinase A and C, also known as Ntrk1 and Ntrk3, respectively) instruct developing neurons to die, both in vitro and in vivo. By contrast, TrkB (also known as Ntrk2), a closely related receptor primarily expressed in the central nervous system, does not. These results indicate that TrkA and TrkC behave as dependence receptors, explaining why developing sympathetic and sensory neurons become trophic-factor-dependent for survival. We suggest that the expansion of the Trk gene family that accompanied the segregation of the peripheral from the central nervous system generated a novel mechanism of cell number control.

Original languageEnglish
Pages (from-to)59-63
Number of pages5
JournalNature
Volume467
Issue number7311
DOIs
StatePublished - 2 Sep 2010
Externally publishedYes

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