Developmental organization of sensory and sympathetic ganglia | Nature

## Summary
Article CAS PubMed PubMed Central Google Scholar Le Douarin, N. Article CAS PubMed PubMed Central Google Scholar Thomas, S. et al. Article CAS PubMed PubMed Central Google Scholar Vincent, E. et al. Article CAS PubMed PubMed Central Google Scholar Baggiolini, A. et al.

## Article Content
Subjects
Cell lineage
Development
Developmental neurogenesis
Abstract
The neural crest generates a broad spectrum of cell types that migrate across the body plan to populate multiple tissues
1
. However, the relationship between lineages of neural crest derivatives remains unclear, and the extent to which neural crest cells delaminated from the neural tube have specified fates remains debated. Here, leveraging CRISPR barcoding in mice and mosaic variant barcode analysis in humans, we demonstrate robust bilateral progenitor clonal spread of neural crest progenitors along the rostrocaudal axis but limited clonal overlap between sensory and sympathetic lineages. Computational modelling of mosaic variants suggests that most neural crest cells show strong fate restriction before delamination. Real-time imaging of quail embryos further shows a fibroblast-growth-factor-dependent rostrocaudal dispersion of neural crest cells across multiple axial levels. These findings support a model in which neural crest fate bias predominantly emerges within the neural tube, with only a minor subset of delaminated progenitors retaining multipotency to generate both sensory and sympathetic derivatives.
Access through your institution
Buy or subscribe
This is a preview of subscription content,
access via your institution
Access options
Access through your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
27,99 €
/ 30 days
cancel any time
Learn more
Subscription info for Korean customers
We have a dedicated website for our Korean customers. Please go to
natureasia.com
to subscribe to this journal.
Go to natureasia.com
Buy this article
Purchase on SpringerLink
Instant access to the full article PDF.
39,95 €
Prices may be subject to local taxes which are calculated during checkout
Fig. 1: Analysis of clonal relationships between DRG and SG by MVBA in mice and humans.
Fig. 2: Spatial distribution of clonal MVs in human DRG and SG.
Fig. 3: DRG and SG are clonally independent tissues in humans.
Fig. 4: NC cell fate specification occurs before left–right determination.
Fig. 5: Rostrocaudal migration across multiple levels distributes clones specific to DRG or SG.
Data availability
Raw whole-genome sequencing, massive parallel amplicon sequencing (MPAS), single-nucleus MPAS (snMPAS), mouse single-cell RNA sequencing and human single-nucleus sequencing data are available from the SRA (accession number
PRJNA799597
); human_g1k_v37 reference genome from
http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/technical/reference/
; gnomAD reference panel from
https://gnomad.broadinstitute.org/
; and mm10 (GRCm38) reference genome from
https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_000001635.20/
.
Code availability
Codes for the data processing and annotation are provided at GitHub (
https://github.com/shishenyxx/Human_DRG_SG
).
References
Bronner, M. E. & LeDouarin, N. M. Development and evolution of the neural crest: an overview.
Dev. Biol.
366
, 2–9 (2012).
Article
CAS
PubMed
PubMed Central
Google Scholar
Le Douarin, N. M. & Dupin, E. The “beginnings” of the neural crest.
Dev. Biol.
444
, S3–S13 (2018).
Article
PubMed
Google Scholar
Le Douarin, N. M. A life in Science with the avian embryo.
Int. J. Dev. Biol.
62
, 19–33 (2018).
Article
PubMed
Google Scholar
Teillet, M. A., Kalcheim, C. & Le Douarin, N. M. Formation of the dorsal root ganglia in the avian embryo: segmental origin and migratory behavior of neural crest progenitor cells.
Dev. Biol.
120
, 329–347 (1987).
Article
CAS
PubMed
Google Scholar
Lallier, T. E. & Bronner-Fraser, M. A spatial and temporal analysis of dorsal root and sympathetic ganglion formation in the avian embryo.
Dev. Biol.
127
, 99–112 (1988).
Article
CAS
PubMed
Google Scholar
Basch, M. L., Bronner-Fraser, M. & Garcia-Castro, M. I. Specification of the neural crest occurs during gastrulation and requires Pax7.
Nature
441
, 218–222 (2006).
Article
ADS
CAS
PubMed
Google Scholar
Hovland, A. S. et al. Pluripotency factors are repurposed to shape the epigenomic landscape of neural crest cells.
Dev. Cell
57
, 2257–2272 (2022).
Article
CAS
PubMed
PubMed Central
Google Scholar
Thomas, S. et al. Human neural crest cells display molecular and phenotypic hallmarks of stem cells.
Hum. Mol. Genet.
17
, 3411–3425 (2008).
Article
CAS
PubMed
PubMed Central
Google Scholar
Weston, J. A. A radioautographic analysis of the migration and localization of trunk neural crest cells in the chick.
Dev. Biol.
6
, 279–310 (1963).
Article
CAS
PubMed
Google Scholar
Noden, D. M. An analysis of migratory behavior of avian cephalic neural crest cells.
Dev. Biol.
42
, 106–130 (1975).
Article
CAS
PubMed
Google Scholar
Serbedzija, G. N., Bronner-Fraser, M. & Fraser, S. E. A vital dye analysis of the timing and pathways of avian trunk neural crest cell migration.
Development
106
, 809–816 (1989).
Article
CAS
PubMed
Google Scholar
Soldatov, R. et al. Spatiotemporal structure of cell fate decisions

---

## Expert Analysis

### Merits
- Here, leveraging CRISPR barcoding in mice and mosaic variant barcode analysis in humans, we demonstrate robust bilateral progenitor clonal spread of neural crest progenitors along the rostrocaudal axis but limited clonal overlap between sensory and sympathetic lineages.
- Computational modelling of mosaic variants suggests that most neural crest cells show strong fate restriction before delamination.
- Unifying comprehensive genomics and transcriptomics in individual cells to illuminate oncogenic and drug resistance mechanisms.
- A robust and high-throughput Cre reporting and characterization system for the whole mouse brain.

### Areas for Consideration
- However, the relationship between lineages of neural crest derivatives remains unclear, and the extent to which neural crest cells delaminated from the neural tube have specified fates remains debated.

### Implications
- Go to natureasia.com Buy this article Purchase on SpringerLink Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Fig. 1: Analysis of clonal relationships between DRG and SG by MVBA in mice and humans.

### Expert Commentary
This article covers pubmed, article, google topics. Notable strengths include discussion of pubmed. Areas of concern are also raised. Readability: Flesch-Kincaid grade 0.0. Word count: 2260.