Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not.
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.
Nikoletopoulou
Vassiliki
V
Biozentrum, University of Basel, CH-4056 Basel, Switzerland. n.vassiliki@unibas.ch
Lickert
Heiko
H
Frade
José Maria
JM
Rencurel
Chantal
C
Giallonardo
Patrizia
P
Zhang
Lixin
L
Bibel
Miriam
M
Barde
Yves-Alain
YA
D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism*; D020812:Receptor, trkC / Q000378:metabolism*
D020917:Receptor, trkA; D020813:Receptor, trkB; D020812:Receptor, trkC
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