RRC ID 40013
Author Banote RK, Edling M, Eliassen F, Kettunen P, Zetterberg H, Abramsson A.
Title β-Amyloid precursor protein-b is essential for Mauthner cell development in the zebrafish in a Notch-dependent manner.
Journal Dev Biol
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.
Volume 413(1)
Pages 26-38
Published 2016-5-1
DOI 10.1016/j.ydbio.2016.03.012
PII S0012-1606(15)30275-X
PMID 26994945
MeSH Amyloid Precursor Protein Secretases / metabolism Amyloid beta-Protein Precursor / metabolism* Animals Behavior, Animal Cell Differentiation Cell Proliferation Dipeptides / chemistry Embryo, Nonmammalian / metabolism Gene Expression Regulation, Developmental* Homeodomain Proteins / metabolism* In Situ Hybridization Microscopy, Fluorescence Morpholinos / metabolism Motor Neurons / metabolism Nerve Tissue Proteins / metabolism* Neurogenesis Neurons / metabolism Oligonucleotides / genetics Oligonucleotides, Antisense / genetics Receptor, Notch1 / metabolism* Receptors, Notch / metabolism Signal Transduction Zebrafish / embryology* Zebrafish / genetics Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 2.896
Times Cited 9
Zebrafish Tg(isl1:GFP)/rw0