Craniofacial muscle development
.
I am a permanent researcher of the French National Center for Scientific Research (CNRS) and working at Pasteur Institute in Paris (France). I am part of the Team "Stem cells and development" headed by Prof. Shahragim Tajbakhsh.
I'm interested in craniofacial muscle biology. Craniofacial
muscles
are the muscles of the head and neck region that constitute about 10%
of body muscles. These muscles are involved
in a number
of crucial non-locomotor
activities,
and are critical
for the most
basic functions
of life, including
chewing,
swallowing,
breathing,
speech, vision as well
as facial expression.
Despite their importance, our understanding of craniofacial muscle biology is still rudimentary, probably due in part to its anatomical complexity. Moreover, development of craniofacial muscles branch out from the traditionally studied limb and trunk muscles, in terms of embryological origins and the associated developmental programs than distinguish them from traditionally studied limb and trunk muscles. In addition, these muscles are also evolutionarily more recent, with some of them being mammal-specific.
It is also intriguing that subsets of craniofacial muscles (in particular the extraocular muscles - EOMs -)
display a
differential
susceptibility
to
dystrophic disease, their resident stem cells
perform differently in vivo and in vitro (in terms of proliferative and self
renewal properties) and the fact that their myofibers express different subset of Myosins and display constant myonuclear turnover. Over
the past years I've been studying skeletal muscle diversity from different
angles.
Projects
1. Emergence and patterning of extraocular muscles (EOMs)
Coordinated development of muscles, tendons, and their attachment sites ensures emergence of functional musculoskeletal units that are adapted to diverse anatomical demands among different species. How these different tissues are patterned and functionally assembled during embryogenesis is poorly understood. We investigated the morphogenesis of EOMs, an evolutionary conserved cranial muscle group. By means of lineage analysis, we redefined the cellular origins of periocular connective tissues interacting with the EOMs, which do not arise exclusively from neural crest mesenchyme as previously thought. Using 3D imaging approaches, we established an integrative blueprint for the EOM functional unit. By doing so, we identified a developmental time window in which individual EOMs emerge from a unique muscle anlage and establish insertions in the sclera, which sets these muscles apart from classical muscle-to-bone type of insertions. Further, we demonstrate that the eyeballs are a source of diffusible all-trans retinoic acid (ATRA) that allow their targeting by the EOMs in a temporal and dose-dependent manner.
2. Colonization of the esophagus by myogenic progenitors
In most vertebrates, the upper digestive tract is composed of muscularized jaws linked to the esophagus that permits food ingestion and swallowing. Esophagus striated muscles (ESM) are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. Using mouse chimeras, we showed that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Further, genetic loss-of-function and pharmacological studies allowed us to demonstrate that MET/HGF signaling is required for antero-posterior migration of esophagus muscle progenitors, where Hgf ligand is expressed in adjacent smooth muscle cells. These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning.
Isl1+ progenitors in the upper esophagus
Confocal imaging of Isl1 progenitors on Isl1Cre:R26mTmG E14.5 embryos
Hgf expression in the bi-layered smooth muscle scaffold
RNAscope in situ hybridization for Hgf (red) and immunostaining for smooth muscle (cyan)
3. Properties of craniofacial muscle stem cells and myofibers
We are using FACS-sorting, myogenic reporters, cell culture and single cell approaches to identify mechanisms regulating the heterogeneity of cranial muscle stem cells and myofibers.
Approach
Techniques and collaborators
confocal microscope and live imaging
morphometric approches (OPT, microCT)
as collaborations (CT Lab Brno, EMBL-Barcelona)
muscle biology
single cell Omics
RNA-scope
mouse genetics
Funding
