RRC ID 12095
Author Lyons DA, Naylor SG, Mercurio S, Dominguez C, Talbot WS.
Title KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome.
Journal Development
Abstract Mutations in Kif1-binding protein/KIAA1279 (KBP) cause the devastating neurological disorder Goldberg-Shprintzen syndrome (GSS) in humans. The cellular function of KBP and the basis of the symptoms of GSS, however, remain unclear. Here, we report the identification and characterization of a zebrafish kbp mutant. We show that kbp is required for axonal outgrowth and maintenance. In vivo time-lapse analysis of neuronal development shows that the speed of early axonal outgrowth is reduced in both the peripheral and central nervous systems in kbp mutants. Ultrastructural studies reveal that kbp mutants have disruption to axonal microtubules during outgrowth. These results together suggest that kbp is an important regulator of the microtubule dynamics that drive the forward propulsion of axons. At later stages, we observe that many affected axons degenerate. Ultrastructural analyses at these stages demonstrate mislocalization of axonal mitochondria and a reduction in axonal number in the peripheral, central and enteric nervous systems. We propose that kbp is an important regulator of axonal development and that axonal cytoskeletal defects underlie the nervous system defects in GSS.
Volume 135(3)
Pages 599-608
Published 2008-2
DOI 10.1242/dev.012377
PII 135/3/599
PMID 18192286
MeSH Abnormalities, Multiple / metabolism* Abnormalities, Multiple / pathology* Animals Axons / metabolism* Axons / ultrastructure Body Patterning Carrier Proteins / genetics Carrier Proteins / metabolism* Cytoskeleton / ultrastructure Enteric Nervous System / embryology Enteric Nervous System / metabolism Enteric Nervous System / ultrastructure Gene Expression Regulation, Developmental Microtubules / metabolism Microtubules / ultrastructure Mitochondria / metabolism Molecular Sequence Data Mutation / genetics Myelin Sheath / ultrastructure Synaptic Vesicles / metabolism Syndrome Zebrafish / embryology Zebrafish / metabolism* Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 5.413
Times Cited 46
Zebrafish rw0130a (Tg (Huc:Kaede))