title: β-Amyloid precursor protein-b is essential for Mauthner cell development in the zebrafish in a Notch-dependent manner.
abstract: Amyloid precursor protein (APP) is a transmembrane glycoprotein that has been the subject of intense research because of its implication in Alzheimer's disease. However, the physiological function of APP in the development and maintenance of the central nervous system remains largely unknown. We have previously shown that the APP homologue in zebrafish (Danio rerio), Appb, is required for motor neuron patterning and formation. Here we study the function of Appb during neurogenesis in the zebrafish hindbrain. Partial knockdown of Appb using antisense morpholino oligonucleotides blocked the formation of the Mauthner neurons, uni- or bilaterally, with an aberrant behavior as a consequence of this cellular change. The Appb morphants had decreased neurogenesis, increased notch signaling and notch1a expression at the expense of deltaA/D expression. The Mauthner cell development could be restored either by a general decrease in Notch signaling through γ-secretase inhibition or by a partial knock down of Notch1a. Together, this demonstrates the importance of Appb in neurogenesis and for the first time shows the essential requirement of Appb in the formation of a specific cell type, the Mauthner cell, in the hindbrain during development. Our results suggest that Appb-regulated neurogenesis is mediated through balancing the Notch1a signaling pathway and provide new insights into the development of the Mauthner cell.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden. Electronic address: rakesh.k.banote@neuro.gu.se.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Banote
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Edling
authors.affiliation: The Faculty of Science, Department of Chemistry and Molecular Biology, University of Gothenburg, 40530 Gothenburg, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Eliassen
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden.
authors.forename: Petronella
authors.initials: P
authors.lastname: Kettunen
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N3BG, United Kingdom.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, S-41345 Gothenburg, Sweden. Electronic address: alexandra.abramsson@neuro.gu.se.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Abramsson
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D002454:Cell Differentiation; D049109:Cell Proliferation; D004151:Dipeptides / Q000737:chemistry; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D060172:Morpholinos / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000235:genetics; D051881:Receptor, Notch1 / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D004151:Dipeptides; D018398:Homeodomain Proteins; D060172:Morpholinos; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D009419:Nerve Tissue Proteins; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D051881:Receptor, Notch1; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C437805:notch1a protein, zebrafish; D053829:Amyloid Precursor Protein Secretases
keywords: APP function; Development; Hindbrain; Mauthner cell; Zebrafish