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LMX1B missense-perturbation of regulatory element footprints disrupt postnatal serotonergic forebrain axon arborization

GSE283961 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/03/12 Platform GPL21626
At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
12 samples: 3 × E17.5 Pet1 neuron control vs 3 × E17.5 Pet1 neuron N246K/+ vs 3 × E17.5 Pet1 neuron R200Q/+ vs 3 × E17.5 Pet1 neuron Delta/+Groups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
LMX1B missense-perturbation of regulatory element footprints disrupts serotonergic forebrain axon arborizationProceedings of the National Academy of Sciences of the United States of America · 2025
Summary (written by the submitters)
Pathogenic coding mutations are prevalent in human neuronal transcription factors (TFs) but how they disrupt development is poorly understood. Lmx1b is a master transcriptional regulator of postmitotic serotonin (5-HT) neuron development; over two hundred pathogenic heterozygous mutations have been discovered in human LMX1B, yet their impact on brain development has not been investigated.
Read the full summary ↓
Here, we developed mouse models with different LMX1B DNA-binding missense mutations. Missense heterozygosity effected highly specific deficits in the postnatal maturation of forebrain serotonin axon arbors, primarily in the hippocampus and motor cortex, which was associated with spatial memory defects. Digital Genomic Footprinting (DGF) revealed that missense heterozygosity caused complete loss of Lmx1b motif protection and chromatin accessibility at sites enriched for a distal active enhancer/active promoter histone signature and homeodomain binding motifs; at other bound Lmx1b motifs, varying levels of losses, gains or unchanged accessibility were found. The spectrum of footprint changes was strongly associated with synapse and axon genes. Lmx1b missense heterozygosity further caused wide disruption of Lmx1b-dependent regulatory networks comprising diverse TFs. These findings suggest Lmx1b missense heterozygosity forces complex dominant negative-like and hypomorphic perturbations on serotonergic regulatory element TF binding and accessibility. Our work illustrates the power of DGF for gaining insight into how TF missense mutations disrupt regulatory networks within neuronal epigenomes.
Published in
LMX1B missense-perturbation of regulatory element footprints disrupts serotonergic forebrain axon arborization
Eastman B, Tabuchi N, Zhang XL et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 40168115 · doi:10.1073/pnas.2411716122
This dataset
Open GSE283961 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE283961_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1196412 and SRA study SRP550564. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40168115) ↗
Study design
3 × E17.5 Pet1 neuron control vs 3 × E17.5 Pet1 neuron N246K/+ vs 3 × E17.5 Pet1 neuron R200Q/+ vs 3 × E17.5 Pet1 neuron Delta/+

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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