title: EGF transactivation of Trk receptors regulates the migration of newborn cortical neurons.
abstract: The development of neuronal networks in the neocortex depends on control mechanisms for mitosis and migration that allow newborn neurons to find their accurate position. Multiple mitogens, neurotrophic factors, guidance molecules and their corresponding receptors are involved in this process, but the mechanisms by which these signals are integrated are only poorly understood. We found that TrkB and TrkC, the receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are activated by epidermal growth factor receptor (EGFR) signaling rather than by BDNF or NT-3 in embryonic mouse cortical precursor cells. This transactivation event regulated migration of early neuronal cells to their final position in the developing cortex. Transactivation by EGF led to membrane translocation of TrkB, promoting its signaling responsiveness. Our results provide genetic evidence that TrkB and TrkC activation in early cortical neurons do not depend on BDNF and NT-3, but instead on transactivation by EGFR signaling.
authors: Institute for Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany.
authors: Dirk
authors: D
authors: Puehringer
authors: Nadiya
authors: N
authors: Orel
authors: Patrick
authors: P
authors: Lüningschrör
authors: Narayan
authors: N
authors: Subramanian
authors: Thomas
authors: T
authors: Herrmann
authors: Moses V
authors: MV
authors: Chao
authors: Michael
authors: M
authors: Sendtner
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000502:physiology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D004815:Epidermal Growth Factor; D020813:Receptor, trkB; D020812:Receptor, trkC