Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish
Precise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit f...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Neural Circuits |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncir.2021.690475/full |
| _version_ | 1818623616890175488 |
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| author | Emilia Asante Devynn Hummel Suman Gurung Suman Gurung Yasmin M. Kassim Noor Al-Shakarji Kannappan Palaniappan Vinoth Sittaramane Anand Chandrasekhar |
| author_facet | Emilia Asante Devynn Hummel Suman Gurung Suman Gurung Yasmin M. Kassim Noor Al-Shakarji Kannappan Palaniappan Vinoth Sittaramane Anand Chandrasekhar |
| author_sort | Emilia Asante |
| collection | DOAJ |
| description | Precise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit function, we studied a zebrafish frizzled3a (fzd3a) loss-of-function mutant off-limits (olt) where the facial branchiomotor (FBM) neurons fail to migrate out of their birthplace. A jaw movement assay, which measures the opening of the zebrafish jaw (gape), showed that the frequency of gape events, but not their amplitude, was decreased in olt mutants. Consistent with this, a larval feeding assay revealed decreased food intake in olt mutants, indicating that the FBM circuit in mutants generates defective functional outputs. We tested various mechanisms that could generate defective functional outputs in mutants. While fzd3a is ubiquitously expressed in neural and non-neural tissues, jaw cartilage and muscle developed normally in olt mutants, and muscle function also appeared to be unaffected. Although FBM neurons were mispositioned in olt mutants, axon pathfinding to jaw muscles was unaffected. Moreover, neuromuscular junctions established by FBM neurons on jaw muscles were similar between wildtype siblings and olt mutants. Interestingly, motor axons innervating the interhyoideus jaw muscle were frequently defasciculated in olt mutants. Furthermore, GCaMP imaging revealed that mutant FBM neurons were less active than their wildtype counterparts. These data show that aberrant positioning of FBM neurons in olt mutants is correlated with subtle defects in fasciculation and neuronal activity, potentially generating defective functional outputs. |
| first_indexed | 2024-12-16T18:43:54Z |
| format | Article |
| id | doaj.art-bf104bf928944a25af5e6d9405f1affd |
| institution | Directory Open Access Journal |
| issn | 1662-5110 |
| language | English |
| last_indexed | 2024-12-16T18:43:54Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj.art-bf104bf928944a25af5e6d9405f1affd2022-12-21T22:20:56ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102021-06-011510.3389/fncir.2021.690475690475Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in ZebrafishEmilia Asante0Devynn Hummel1Suman Gurung2Suman Gurung3Yasmin M. Kassim4Noor Al-Shakarji5Kannappan Palaniappan6Vinoth Sittaramane7Anand Chandrasekhar8Division of Biological Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, United StatesDivision of Biological Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, United StatesDivision of Biological Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, United StatesDepartment of Pathology and Cell Biology, USF Health Heart Institute, University of South Florida, Tampa, Florida, FL, United StatesComputational Imaging and VisAnalysis (CIVA) Lab, Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, United StatesComputational Imaging and VisAnalysis (CIVA) Lab, Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, United StatesComputational Imaging and VisAnalysis (CIVA) Lab, Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, United StatesDepartment of Biology, Georgia Southern University, Statesboro, GA, United StatesDivision of Biological Sciences and Bond Life Sciences Center, University of Missouri, Columbia, MO, United StatesPrecise positioning of neurons resulting from cell division and migration during development is critical for normal brain function. Disruption of neuronal migration can cause a myriad of neurological disorders. To investigate the functional consequences of defective neuronal positioning on circuit function, we studied a zebrafish frizzled3a (fzd3a) loss-of-function mutant off-limits (olt) where the facial branchiomotor (FBM) neurons fail to migrate out of their birthplace. A jaw movement assay, which measures the opening of the zebrafish jaw (gape), showed that the frequency of gape events, but not their amplitude, was decreased in olt mutants. Consistent with this, a larval feeding assay revealed decreased food intake in olt mutants, indicating that the FBM circuit in mutants generates defective functional outputs. We tested various mechanisms that could generate defective functional outputs in mutants. While fzd3a is ubiquitously expressed in neural and non-neural tissues, jaw cartilage and muscle developed normally in olt mutants, and muscle function also appeared to be unaffected. Although FBM neurons were mispositioned in olt mutants, axon pathfinding to jaw muscles was unaffected. Moreover, neuromuscular junctions established by FBM neurons on jaw muscles were similar between wildtype siblings and olt mutants. Interestingly, motor axons innervating the interhyoideus jaw muscle were frequently defasciculated in olt mutants. Furthermore, GCaMP imaging revealed that mutant FBM neurons were less active than their wildtype counterparts. These data show that aberrant positioning of FBM neurons in olt mutants is correlated with subtle defects in fasciculation and neuronal activity, potentially generating defective functional outputs.https://www.frontiersin.org/articles/10.3389/fncir.2021.690475/fulljaw movementfood intakebehaviorneuronal migrationaxon guidancezebrafish |
| spellingShingle | Emilia Asante Devynn Hummel Suman Gurung Suman Gurung Yasmin M. Kassim Noor Al-Shakarji Kannappan Palaniappan Vinoth Sittaramane Anand Chandrasekhar Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish Frontiers in Neural Circuits jaw movement food intake behavior neuronal migration axon guidance zebrafish |
| title | Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish |
| title_full | Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish |
| title_fullStr | Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish |
| title_full_unstemmed | Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish |
| title_short | Defective Neuronal Positioning Correlates With Aberrant Motor Circuit Function in Zebrafish |
| title_sort | defective neuronal positioning correlates with aberrant motor circuit function in zebrafish |
| topic | jaw movement food intake behavior neuronal migration axon guidance zebrafish |
| url | https://www.frontiersin.org/articles/10.3389/fncir.2021.690475/full |
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