Time‐sequenced transcriptomes of developing distal mouse limb buds: A comparative tissue layer analysis

Abstract

Background: The development of the amniote limb has been an important model system to study patterning mechanisms and morphogenesis. For proper growth and patterning, it requires the interaction between the distal sub-apical mesenchyme and the apical ectodermal ridge (AER) that involve the separate implementation of coordinated and tissue-specific genetic programs. Results: Here, we produce and analyze the transcriptomes of both distal limb mesenchymal progenitors and the overlying ectodermal cells, following timecoursed dissections that cover from limb bud initiation to fully patterned limbs. The comparison of transcriptomes within each layer as well as between layers over time, allowed the identification of specific transcriptional signatures for each of the developmental stages. Special attention was given to the identification of genes whose transcription dynamics suggest a previously unnoticed role in the context of limb development and also to signaling pathways enriched between layers. Conclusion:We interpret the transcriptomic data in light of the known development pattern and we conclude that a major transcriptional transition occurs in distal limb buds between E9.5 and E10.5, coincident with the switch from an early phase continuation of the signature of trunk progenitors, related to the initial proximo distal specification, to a late intrinsic phase of development.

GLI transcriptional repression is inert prior to Hedgehog pathway activation

“…3b, c). This would be consistent with recent findings that the early limb transcriptome is a continuation of that observed in trunk progenitors 38 . We conclude that GLI3 is unlikely to be engaged in ongoing transcriptional repression in the early limb bud.…”

Limb development, evolution, and regeneration and repair: Part two

“…This is in stark contrast with the current view that Grem1 downregulation triggers the termination of the limb outgrowth. This conclusion is indeed supported by Fernandez-Guerrero et al, 3 in this issue, who analyze the transcriptome of distal mouse limb mesenchyme and ectoderm across different stages. Their analyses, which show that a transcriptional transition operates between E9.5 and E10.5, does not support a role for Grem1 in the termination of limb outgrowth.…”

A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors

“…3 N,O, Table S3J,K). Additionally, the few Mesp1 KO cells present in the postLPM cluster showed upregulation of genes involved in mesendoderm specification and organization ( Lhx1 , Eomes , Asb4 ) ( Fernandez-Guerrero et al, 2021 ) and downregulation of, or a lack of, patterning, morphogenesis and maturation genes ( Crabp1 , Foxc2 , Meis2 ) ( Fig. 3 P, Table S3L).…”