ZFIN ID: ZDB-PUB-080209-11
KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome
Lyons, D.A., Naylor, S.G., Mercurio, S., Dominguez, C., and Talbot, W.S.
Date: 2008
Source: Development (Cambridge, England)   135(3): 599-609 (Journal)
Registered Authors: Dominguez, Claudia, Lyons, David A., Mercurio, Sara, Naylor, Stephen, Talbot, William S.
Keywords: Kif1-binding protein, Axonal outgrowth, Mental retardation, Neurodegeneration, Zebrafish
MeSH Terms:
  • 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*
PubMed: 18192286 Full text @ Development
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.