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Development. 2018 Sep 20;145(18). pii: dev160945. doi: 10.1242/dev.160945.

Divergent early mesoderm specification underlies distinct head and trunk muscle programmes in vertebrates.

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Institute for Stem Cell Biology and Regenerative Medicine, GKVK Campus, Bellary Road, Bengaluru 560065, India.
SASTRA University, Thirumalaisamudram, Thanjavur 613401, India.
Manipal Academy of Higher Education, Manipal 576104, India.
National Centre for Biological Sciences, TIFR, GKVK Campus, Bellary Road, Bengaluru 560065, India.
Institute for Stem Cell Biology and Regenerative Medicine, GKVK Campus, Bellary Road, Bengaluru 560065, India


Head and trunk muscles have discrete embryological origins and are governed by distinct regulatory programmes. Whereas the developmental route of trunk muscles from mesoderm is well studied, that of head muscles is ill defined. Here, we show that, unlike the myogenic trunk paraxial mesoderm, head mesoderm development is independent of the T/Tbx6 network in mouse. We reveal that, in contrast to Wnt and FGF-driven trunk mesoderm, dual inhibition of Wnt/β-catenin and Nodal specifies head mesoderm. Remarkably, the progenitors derived from embryonic stem cells by dual inhibition efficiently differentiate into cardiac and skeletal muscle cells. This twin potential is the defining feature of cardiopharyngeal mesoderm: the head subtype giving rise to heart and branchiomeric head muscles. Therefore, our findings provide compelling evidence that dual inhibition specifies head mesoderm and unravel the mechanism that diversifies head and trunk muscle programmes during early mesoderm fate commitment. Significantly, this is the first report of directed differentiation of pluripotent stem cells, without transgenes, into progenitors with muscle/heart dual potential. Ability to generate branchiomeric muscle in vitro could catalyse efforts in modelling myopathies that selectively involve head muscles.


Cardiopharyngeal mesoderm; Cranial mesoderm; Head muscles; Skeletal muscle differentiation; Tbx6; Wnt inhibition


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