| RRC ID |
12095
|
| 著者 |
Lyons DA, Naylor SG, Mercurio S, Dominguez C, Talbot WS.
|
| タイトル |
KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome.
|
| ジャーナル |
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.
|
| 巻・号 |
135(3)
|
| ページ |
599-608
|
| 公開日 |
2008-2-1
|
| 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 |
5.611
|
| 引用数 |
54
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
|
| リソース情報 |
| ゼブラフィッシュ |
rw0130a (Tg (Huc:Kaede)) |
