title: Oculomotor instabilities in zebrafish mutant belladonna: a behavioral model for congenital nystagmus caused by axonal misrouting.
abstract: A large fraction of homozygous zebrafish mutant belladonna (bel) larvae display a reversed optokinetic response (OKR) that correlates with failure of the retinal ganglion cells to cross the midline and form the optic chiasm. Some of these achiasmatic mutants display strong spontaneous eye oscillations (SOs) in the absence of motion in the surround. The presentation of a stationary grating was necessary and sufficient to evoke SO. Both OKR reversal and SO depend on vision and are contrast sensitive. We built a quantitative model derived from bel fwd (forward) eye behaviors. To mimic the achiasmatic condition, we reversed the sign of the retinal slip velocity in the model, thereby successfully reproducing both reversed OKR and SO. On the basis of the OKR data, and with the support of the quantitative model, we hypothesize that the reversed OKR and the SO can be completely attributed to RGC misrouting. The strong resemblance between the SO and congenital nystagmus (CN) seen in humans with defective retinotectal projections implies that CN, of so far unknown etiology, may be directly caused by a projection defect.
authors.affiliation: Institute of Zoology, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Huang
authors.forename: Oliver
authors.initials: O
authors.lastname: Rinner
authors.forename: Patrik
authors.initials: P
authors.lastname: Hedinger
authors.forename: Shih-Chii
authors.initials: SC
authors.lastname: Liu
authors.forename: Stephan C F
authors.initials: SC
authors.lastname: Neuhauss
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D003198:Computer Simulation; D015350:Contrast Sensitivity / Q000235:genetics / Q000502:physiology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005133:Eye Movements / Q000235:genetics / Q000502:physiology; D060850:LIM-Homeodomain Proteins; D007814:Larva; D008959:Models, Neurological; D009024:Morphogenesis / Q000235:genetics; D009039:Motion Perception / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D017120:Nystagmus, Optokinetic / Q000235:genetics / Q000502:physiology*; D009759:Nystagmus, Pathologic / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D009897:Optic Chiasm / Q000473:pathology*; D010775:Photic Stimulation; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014157:Transcription Factors; D015027:Zebrafish / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C509734:lhx2b protein, zebrafish