PUBLICATION
Loss of autism-candidate CHD8 perturbs neural crest development and intestinal homeostatic balance
- Authors
- Hayot, G., Massonot, M., Keime, C., Faure, E., Golzio, C.
- ID
- ZDB-PUB-221115-77
- Date
- 2022
- Source
- Life science alliance 6(1): (Journal)
- Registered Authors
- Keywords
- none
- Datasets
- GEO:GSE184359, GEO:GSE184364, GEO:GSE184363
- MeSH Terms
-
- Animals
- Autistic Disorder*
- Cell Movement/genetics
- Homeostasis
- Intestines
- Neural Crest*/metabolism
- Serotonin/metabolism
- Zebrafish
- PubMed
- 36375841 Full text @ Life Sci Alliance
Citation
Hayot, G., Massonot, M., Keime, C., Faure, E., Golzio, C. (2022) Loss of autism-candidate CHD8 perturbs neural crest development and intestinal homeostatic balance. Life science alliance. 6(1):.
Abstract
Individuals with mutations in CHD8 present with gastrointestinal complaints, yet the underlying mechanisms are understudied. Here, using a stable constitutive chd8 mutant zebrafish model, we found that the loss of chd8 leads to a reduced number of vagal neural crest cells (NCCs), enteric neural and glial progenitors, emigrating from the neural tube, and that their early migration capability was altered. At later stages, although the intestinal colonization by NCCs was complete, we found the decreased numbers of both serotonin-producing enterochromaffin cells and NCC-derived serotonergic neurons, suggesting an intestinal hyposerotonemia in the absence of chd8 Furthermore, transcriptomic analyses revealed an altered expression of key receptors and enzymes in serotonin and acetylcholine signaling pathways. The tissue examination of chd8 mutants revealed a thinner intestinal epithelium accompanied by an accumulation of neutrophils and the decreased numbers of goblet cells and eosinophils. Last, single-cell sequencing of whole intestines showed a global disruption of the immune balance with a perturbed expression of inflammatory interleukins and changes in immune cell clusters. Our findings propose a causal developmental link between chd8, NCC development, intestinal homeostasis, and autism-associated gastrointestinal complaints.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping