Yvernogeau, L. | Search bioRxiv

bioRxiv2020

Generation of a new Tbx6-inducible reporter mouse line to trace presomitic mesoderm derivatives throughout development and in adults

The presomitic mesoderm (PSM) is initially an unsegmented structure localized on each side of the neural tube of the developing embryo, which progressively segments to form the somites. The somites will segregate and partition to generate the dorsal dermomyotome and the ventral sclerotome. Endothelial and myogenic cells of both the trunk and limbs are derived from the somites. There is a lack of efficient reporter mouse models to label and trace the PSM derivatives, despite their crucial contribution to many developmental processes. In this study, we generated a tamoxifen inducible transgenic Tbx6 mouse line, Tg(Tbx6_Cre/ERT2)/ROSA-eYFP, to tag and follow PSM-derivatives from early embryonic stages until adulthood. After induction, endothelial and myogenic cells can be easily identified within the trunk and limbs with proper expression patterns. Since our Tg(Tbx6_Cre/ERT2)/ROSA-eYFP model allows to permanently label the PSM-derived cells, their progeny can be studied at long-term, opening the possibility to perform lineage tracing of stem cells upon aging.

developmental biology↗

bioRxiv2020

BMP signalling directs a fibroblast-to-myoblast conversion at the connective tissue/muscle interface to pattern limb muscles

Positional information driving limb muscle patterning is contained in lateral plate mesoderm-derived tissues, such as tendon or muscle connective tissue but not in myogenic cells themselves. The long-standing consensus is that myogenic cells originate from the somitic mesoderm, while connective tissue fibroblasts originate from the lateral plate mesoderm. We challenged this model using cell and genetic lineage tracing experiments in birds and mice, respectively, and identified a subpopulation of myogenic cells at the muscle tips close to tendons originating from the lateral plate mesoderm and derived from connective tissue gene lineages. Analysis of single-cell RNA-sequencing data obtained from limb cells at successive developmental stages revealed a subpopulation of cells displaying a dual muscle and connective tissue signature, in addition to independent muscle and connective tissue populations. Active BMP signalling was detected in this junctional cell sub-population and at the tendon/muscle interface in developing limbs. BMP gain- and loss-of-function experiments performed in vivo and in vitro showed that this signalling pathway regulated a fibroblast-to-myoblast conversion. We propose that localised BMP signalling converts a subset of lateral plate mesoderm-derived fibroblasts to a myogenic fate and establishes a boundary of fibroblast-derived myonuclei at the muscle/tendon interface to control the muscle pattern during limb development.

developmental biology↗