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.

Lyons, D., Naylor, S., Mercurio, S., Dominguez, C., Talbot, W. (2008). KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome. DEVELOPMENT, 135(3), 599-608 [10.1242/dev.012377].

KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome

MERCURIO, SARA;
2008

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.
Articolo in rivista - Articolo scientifico
Axonal outgrowth; Kif1-binding protein; Mental retardation; Neurodegeneration; Zebrafish; Abnormalities, Multiple; Animals; Axons; Body Patterning; Carrier Proteins; Cytoskeleton; Enteric Nervous System; Gene Expression Regulation, Developmental; Microtubules; Mitochondria; Molecular Sequence Data; Mutation; Myelin Sheath; Synaptic Vesicles; Syndrome; Zebrafish; Zebrafish Proteins; Cell Biology; Developmental Biology; Molecular Biology; Anatomy
English
599
608
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Lyons, D., Naylor, S., Mercurio, S., Dominguez, C., Talbot, W. (2008). KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome. DEVELOPMENT, 135(3), 599-608 [10.1242/dev.012377].
Lyons, D; Naylor, S; Mercurio, S; Dominguez, C; Talbot, W
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/105797
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