Coordination of early neural tube development by BDNF/trkB.
Neurotrophins signal through members of the trk family of tyrosine kinase receptors and are known to regulate several neuronal properties. Although initially characterized by their ability to prevent naturally occurring cell death of subsets of neurons during development, neurotrophins can also regulate the proliferation and differentiation of precursor cells. Here we report a novel involvement of neurotrophins in early development of the neural tube. We demonstrate that a functional trkB receptor is expressed by motor neuron progenitors in the ventral neural tube and that treatment of ventral neural tube explants with the trkB ligand Brain-Derived Neurotrophic Factor (BDNF) leads to a significant increase in the number of motor neurons. The only BDNF expression detectable at this stage is by a subset of ventrally projecting interneurons in the dorsal neural tube; ablating this region in vivo leads to a reduction of motor neuron numbers. This loss can be prevented by simultaneous treatment with BDNF. We propose that BDNF produced by dorsal interneurons stimulates proliferation and/or differentiation of motor neuron progenitors after anterograde axonal transport and release in proximity to the trkB-expressing motor neuron precursors, thereby coordinating development between dorsal and ventral regions of the neural tube.
Jungbluth
S
S
Department of Developmental Neurobiology, United Medical and Dental School, Guy's Hospital, London, UK.
Koentges
G
G
Lumsden
A
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000494:pharmacology*; D002455:Cell Division; D002490:Central Nervous System / Q000737:chemistry / Q000166:cytology / Q000196:embryology*; D002642:Chick Embryo; D046508:Culture Techniques; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D007395:Interneurons / Q000737:chemistry; D060850:LIM-Homeodomain Proteins; D009046:Motor Neurons / Q000737:chemistry* / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009672:Notochord / Q000502:physiology / Q000637:transplantation; D012333:RNA, Messenger / Q000032:analysis; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis* / Q000235:genetics; D012249:Rhombencephalon / Q000502:physiology; D013234:Stem Cells; D014157:Transcription Factors
D019208:Brain-Derived Neurotrophic Factor; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1