A transcriptional and regulatory map of mouse somitogenesis

Background

The vertebrate body plan undergoes a process of segmentation during embryonic development. This segmentation results in the formation of somites, which are structures that form from the presomitic mesoderm (located in the posterior part of the embryo) on both sides of the neural tube. Each pair of somites is formed rhythmically along the anterior-posterior axis following the cyclic transcription of certain genes in the presomitic mesoderm [1].

Somitogenesis has been extensively studied to decipher the identity of the oscillatory genes that drive the formation of the somites, their specification, or the establishment of the boundaries. The morphological aspect of each newly formed pair of somites is very similar. However, they are built at different times and occupy different spatial locations along the anterior-posterior axis. Ibarra-Soria and colleagues focused on understanding the spatiotemporal regulation of mouse somitogenesis by performing RNA-seq and ATAC-seq in individual, microdissected somites. The authors analysed the three most recently formed somites at six developmental stages to characterise the common aspects associated with somite formation and maturation independently of their stage as well as the differences between stages that could give insights into the spatial identity of each pair of somites.

 

Key findings

• Newly formed somites progress towards epithelial-to-mesenchymal transition. To understand the changes that characterise the maturation of newly formed somites, the authors performed pairwise comparisons of the three most recently formed somites regardless of their developmental stage. Genes enriched in the less mature somites were associated with the presomitic mesoderm and somite segmentation (including members of the Wnt and Notch signalling pathways), while genes enriched in the more matured somites indicated activation of adhesion and migration programmes. Changes in chromatin accessibility pointed towards the same programmes. Interestingly, most chromatin changes were associated with enhancer-like regions rather than promoters.

 

• Early and late somites activate different programmes according to their spatiotemporal context. Somites located at different positions along the anteroposterior axis will have a specific identity and will give rise to different derivatives. To address if these differences were already emerging in the newly formed somites, the authors compared the data obtained from different developmental time points. Gene Ontology enrichment analyses showed that somites that occupy different locations along the anteroposterior axis in the embryo have distinct functional terms. For instance, thoracic somites were enriched for genes associated with muscle and cartilage lineages while sacral somites showed an enrichment for genes involved in blood vessel remodelling. The chromatin landscape also showed extensive changes according to their developmental stage and, in this case, a higher proportion of open chromatin regions was associated with promoters.

 

 

• Somite differentiation accelerates at late developmental stages. The authors observed that the accessibility of chromatin was higher at later developmental stages as well as the expression levels of key transcription factors including members of Smad and Bmp families. They suggest that higher levels of some of these factors could be responsible for the activation of more mature programmes.

 

Why I chose this preprint

I am very interested in the progression of development in vertebrates and how the maturation of different tissues is regulated. I really liked the idea of using somitogenesis to address the question of how the same tissue can mature in a different way depending on the spatiotemporal context.

Also, I really appreciate the challenge of using low-input material (both from a dissection and an omics point of view) and this work encourages us to think about the questions that we can address in vivo.

 

Questions to the authors

• One of the most interesting results of the changes in chromatin accessibility is that the activation of the maturation programme independently of the developmental stage entails changes in distal regulatory elements. In contrast, chromatin remodelling associated with stage-specific changes affects promoter and proximal regions. Do the authors think that promoters of genes associated with the common maturation programme are already accessible since the beginning and they just need the activation of enhancer-like elements to modulate their expression and progress in the maturation cascade?

 

• I find it very interesting how newly formed somites at late stages seem to mature more quickly. The authors suggest that this is accompanied by a more permissive state of the chromatin (and higher levels of expression of key factors). It has been shown that the rate of somite formation slows down while development progresses [1]. Do the authors think that the fact that it takes longer for posterior somites to form could mean they have more time to undergo changes in the chromatin while being formed and, as a consequence, be more ready and able to mature faster?

 

References

1. Palmeirim et al (1993). Avian hairy Gene Expression Identifies a Molecular Clock Linked to Vertebrate Segmentation and Somitogenesis. Cell 91(5):639-648.
2. Tam (1981). The control of somitogenesis in mouse embryos. Development 65:103-128.

Tags: atac-seq, mouse, rna-seq, somitogenesis

doi: https://doi.org/10.1242/prelights.33795

Read preprint (No Ratings Yet)