title: Notch signaling controls generation of motor neurons in the lesioned spinal cord of adult zebrafish.
abstract: In mammals, increased Notch signaling is held partly responsible for a lack of neurogenesis after a spinal injury. However, this is difficult to test in an essentially nonregenerating system. We show that in adult zebrafish, which exhibit lesion-induced neurogenesis, e.g., of motor neurons, the Notch pathway is also reactivated. Although apparently compatible with neuronal regeneration in zebrafish, forced activity of the pathway significantly decreased progenitor proliferation and motor neuron generation. Conversely, pharmacological inhibition of the pathway increased proliferation and motor neuron numbers. This demonstrates that Notch is a negative signal for regenerative neurogenesis, and, importantly, that spinal motor neuron regeneration can be augmented in an adult vertebrate by inhibiting Notch signaling.
authors.affiliation: Centre for Neuroregeneration, School of Biomedical Sciences, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
authors.forename: Tatyana B
authors.initials: TB
authors.lastname: Dias
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Yang
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogai
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Catherina G
authors.initials: CG
authors.lastname: Becker
mesh_terms: D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D018398:Homeodomain Proteins / Q000502:physiology*; D008297:Male; D009046:Motor Neurons / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D051881:Receptor, Notch1 / Q000502:physiology*; D051880:Receptors, Notch / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051881:Receptor, Notch1; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C437805:notch1a protein, zebrafish