PUBLICATION

16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis

Authors
Tomasello, D.L., Kim, J.L., Khodour, Y., McCammon, J.M., Mitalipova, M., Jaenisch, R., Futerman, A.H., Sive, H.
ID
ZDB-PUB-220106-2
Date
2021
Source
iScience   25: 103551 (Journal)
Registered Authors
McCammon, Jasmine, Sive, Hazel
Keywords
Cellular neuroscience, Developmental neuroscience, Molecular neuroscience, Neuroscience
MeSH Terms
none
PubMed
34984324 Full text @ iScience
Abstract
The complex 16p11.2 deletion syndrome (16pdel) is accompanied by neurological disorders, including epilepsy, autism spectrum disorder, and intellectual disability. We demonstrated that 16pdel iPSC differentiated neurons from affected people show augmented local field potential activity and altered ceramide-related lipid species relative to unaffected. FAM57B, a poorly characterized gene in the 16p11.2 interval, has emerged as a candidate tied to symptomatology. We found that FAM57B modulates ceramide synthase (CerS) activity, but is not a CerS per se. In FAM57B mutant human neuronal cells and zebrafish brain, composition and levels of sphingolipids and glycerolipids associated with cellular membranes are disrupted. Consistently, we observed aberrant plasma membrane architecture and synaptic protein mislocalization, which were accompanied by depressed brain and behavioral activity. Together, these results suggest that haploinsufficiency of FAM57B contributes to changes in neuronal activity and function in 16pdel syndrome through a crucial role for the gene in lipid metabolism.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
Fish Conditions Stage Phenotype Figure
ABchemical treatment by environment: pentetrazolDays 7-13
tlcd3bbzf3799/+; tlcd3bazf3800/+ (AB)standard conditionsDays 7-13
tlcd3bbzf3799/+; tlcd3bazf3800/+ (AB)standard conditionsDays 7-13
tlcd3bbzf3799/+; tlcd3bazf3800/+ (AB)standard conditionsDays 7-13
tlcd3bbzf3799/+; tlcd3bazf3800/+ (AB)standard conditionsDays 7-13
tlcd3bbzf3799/+; tlcd3bazf3800/+ (AB)standard conditionsDays 7-13
tlcd3bbzf3799/+; tlcd3bazf3800/+ (AB)standard conditionsDays 7-13
tlcd3bbzf3799/zf3799; tlcd3bazf3800/zf3800 (AB)controlDays 7-13
tlcd3bbzf3799/zf3799; tlcd3bazf3800/zf3800 (AB)controlDays 7-13
tlcd3bbzf3799/zf3799; tlcd3bazf3800/zf3800 (AB)controlDays 7-13
1 - 10 of 28
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zf3799
    		Small Deletion
    zf3800
      		Unknown
      1 - 2 of 2
      Show
      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      tlcd3baTALEN1-tlcd3baTALEN
      tlcd3bbCRISPR1-tlcd3bbCRISPR
      1 - 2 of 2
      Show
      Fish
      Fish
      AB
      tlcd3bbzf3799/+; tlcd3bazf3800/+ (AB)
      tlcd3bbzf3799/zf3799; tlcd3bazf3800/zf3800 (AB)
      1 - 3 of 3
      Show
      Antibodies
      Name Type Antigen Genes Isotypes Host Organism
      Ab1-gadpolyclonal
        		Rabbit
        Ab4-syt1polyclonal
          		IgGRabbit
          Ab6-actbmonoclonal
            		IgMMouse
            1 - 3 of 3
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            Orthology
            No data available
            Engineered Foreign Genes
            No data available
            Mapping
            No data available
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            Citation
            Tomasello, D.L., Kim, J.L., Khodour, Y., McCammon, J.M., Mitalipova, M., Jaenisch, R., Futerman, A.H., Sive, H. (2021) 16pdel lipid changes in iPSC-derived neurons and function of FAM57B in lipid metabolism and synaptogenesis. iScience. 25:103551.