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GEO Series: GSE155553

Title: Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience [Xenopus]

Summary

Gene Ontology analyses of autism spectrum disorders (ASD) risk genes have repeatedly highlighted synaptic function and transcriptional regulation as key points of convergence. However, these analyses rely on incomplete knowledge of gene function across brain development. Here we leverage Xenopus tropicalis to study in vivo ten genes with the strongest statistical evidence for association with ASD. All genes are expressed in developing telencephalon at time points mapping to human mid-prenatal development, and mutations lead to an increase in the ratio of neural progenitor cells to maturing neurons, supporting previous in silico systems biological findings implicating cortical neurons in ASD vulnerability, but expanding the range of convergent functions to include neurogenesis. Systematic chemical screening identifies that estrogen, via Sonic hedgehog signaling, rescues this convergent phenotype in Xenopus and human models of brain development, suggesting a resilience factor that may mitigate a range of ASD genetic risks.


Contributors: Arthur Willsey, Helen Willsey, A Willsey

Experiment Type: 3 pooled stage 46 brains in triplicate. DMSO-treated samples are the controls.

Experiment Reagents: Cyclopamine, estradiol.

Phenotypes:
Xtr Wt + CYCLOPAMINE + brain NF46 (RNA-Seq (RNA))

Article: XB-ART-57754, PubMed

Source: NCBI GEO, Xenbase Download

Samples: (DEG = Differentially Expressed Genes; GSM = GEO Sample Number)
Sample View GSMs Assay Type
brain - NF46 GSM4706053  GSM4706054  GSM4706055  RNA-Seq
Background: Xtr.NigerianNasco
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 46  
   brain + CYCLOPAMINE - NF46 DEG GSM4706050  GSM4706051  GSM4706052  RNA-Seq
Background: Xtr.NigerianNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
chemical Cyclopamine NF stage 29 and 30 embryo
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 46  
   brain + estradiol - NF46 DEG GSM4706047  GSM4706048  GSM4706049  RNA-Seq
Background: Xtr.NigerianNasco
Manipulations:
Manipulation Type Reagent Target Gene Stage Treatment Area
chemical estradiol NF stage 29 and 30 embryo
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 46  
brain - NF40 GSM4706056  GSM4706057  GSM4706058  RNA-Seq
Background: Xtr.NigerianNasco
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 40  
brain - NF42 GSM4706059  GSM4706060  GSM4706061  RNA-Seq
Background: Xtr.NigerianNasco
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 42  
brain - NF44 GSM4706062  GSM4706063  GSM4706064  RNA-Seq
Background: Xtr.NigerianNasco
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 44  
brain - NF45 GSM4706065  GSM4706066  GSM4706067  RNA-Seq
Background: Xtr.NigerianNasco
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 45  
brain - NF46 GSM4706068  GSM4706069  GSM4706070  RNA-Seq
Background: Xtr.NigerianNasco
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 46  
brain - NF47 GSM4706071  GSM4706072  GSM4706073  RNA-Seq
Background: Xtr.NigerianNasco
Conditions:
Tissue Assay Stages ChIP Antibody
brain NF stage 47  
Select All DEG      Select All 
Xtr   
Xla 

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