PUBLICATION
Zebrafish dscaml1 Deficiency Impairs Retinal Patterning and Oculomotor Function
- Authors
- Ma 马漫修, M., Ramirez, A.D., Wang 王彤, T., Roberts, R.L., Harmon, K.E., Schoppik, D., Sharma, A., Kuang, C., Goei, S.L., Gagnon, J.A., Zimmerman, S., Tsai, S.Q., Reyon, D., Joung, J.K., Aksay, E.R.F., Schier, A.F., Pan 潘於勤, Y.A.
- ID
- ZDB-PUB-191108-5
- Date
- 2019
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 40(1): 143-158 (Journal)
- Registered Authors
- Pan, Y. Albert, Schier, Alexander, Schoppik, David, Zimmerman, Steve
- Keywords
- none
- MeSH Terms
-
- Adaptation, Ocular/genetics
- Adaptation, Ocular/physiology
- Amacrine Cells/physiology
- Animals
- Animals, Genetically Modified
- Calcium Signaling
- Cell Adhesion Molecules/physiology
- Eye Movements/genetics
- Eye Movements/physiology*
- Fixation, Ocular/genetics
- Fixation, Ocular/physiology
- Larva
- Locomotion
- Muscle Fatigue
- Mutation
- Oculomotor Muscles/growth & development
- Oculomotor Muscles/physiopathology
- Retina/growth & development
- Retina/ultrastructure
- Saccades/genetics
- Saccades/physiology
- Zebrafish/growth & development
- Zebrafish Proteins/physiology
- PubMed
- 31685652 Full text @ J. Neurosci.
Citation
Ma 马漫修, M., Ramirez, A.D., Wang 王彤, T., Roberts, R.L., Harmon, K.E., Schoppik, D., Sharma, A., Kuang, C., Goei, S.L., Gagnon, J.A., Zimmerman, S., Tsai, S.Q., Reyon, D., Joung, J.K., Aksay, E.R.F., Schier, A.F., Pan 潘於勤, Y.A. (2019) Zebrafish dscaml1 Deficiency Impairs Retinal Patterning and Oculomotor Function. The Journal of neuroscience : the official journal of the Society for Neuroscience. 40(1):143-158.
Abstract
Down Syndrome Cell Adhesion Molecules (dscam and dscaml1) are essential regulators of neural circuit assembly, but their roles in vertebrate neural circuit function are still mostly unexplored. We investigated the functional consequences of dscaml1 deficiency in the larval zebrafish (sexually undifferentiated) oculomotor system, where behavior, circuit function, and neuronal activity can be precisely quantified. Genetic perturbation of dscaml1 resulted in deficits in retinal patterning and light adaptation, consistent with its known roles in mammals. Oculomotor analyses revealed specific deficits related to the dscaml1 mutation, including severe fatigue during gaze stabilization, reduced saccade amplitude and velocity in the light, greater disconjugacy, and impaired fixation. Two-photon calcium imaging of abducens neurons in control and dscaml1 mutant animals confirmed deficits in saccade-command signals (indicative of an impairment in the saccadic premotor pathway), while abducens activation by the pretectum-vestibular pathway was not affected. Together, we show that loss of dscaml1 resulted in impairments in specific oculomotor circuits, providing a new animal model to investigate the development of oculomotor premotor pathways and their associated human ocular disorders.SIGNIFICANCE STATEMENTDscaml1 is a neural developmental gene with unknown behavioral significance. Using the zebrafish model, this study shows that dscaml1 mutants have a host of oculomotor (eye movement) deficits. Notably, the oculomotor phenotypes in dscaml1 mutants are reminiscent of human ocular motor apraxia, a neurodevelopmental disorder characterized by reduced saccade amplitude and gaze stabilization deficits. Population-level recording of neuronal activity further revealed potential subcircuit-specific requirements for dscaml1 during oculomotor behavior. These findings underscore the importance of dscaml1 in the development of visuomotor function and characterize a new model to investigate potential circuit deficits underlying human oculomotor disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping