Research / Scientific departments / Developmental Biology / Units and groups / Stem cells and development

Stems Cells and Development (URA CNRS 2578)

Shahragim Tajbakhsh 
shaht@pasteur.fr

Establishing the skeletal muscle lineage

How do stem cells self-renew and establish skeletal muscle during embryonic and fœtal development, and in the adult (1)? We have developed unique genetic tools by knock-ins and transgenesis to address this issue in the mouse.
shah-fig1

Specification and determination of skeletal muscle

We showed previously that Pax3 and Myf5 are key transcription factors acting genetically upstream of Myod to establish skeletal muscle in the body (1). More recently, our work has extended these observations and lead to a revision of the long standing view that Myf5 and Myod are the only determination genes in this lineage in mice. Unexpectedly, Mrf4 which was previously described as a differentiation gene, acts as a determination gene in vivo. Consequently, Mrf4:Myf5:Myod triple mutants are required to eliminate all skeletal muscle in the mouse (2). Importantly, the new Myf5:Myod double mutants permit us to genetically uncouple embryonic from fœtal myogenesis and ask how skeletal muscle stem and progenitor cells which are marked by Pax3 and Pax7 expression, self-renew and regulate this lineage.

Asymmetric cell divisions and stem cell self-renewal

One mechanism governing stem cell self-renewal involves asymmetric cell divisions. Using live imaging and videomicroscopy in combination with immunochemistry of the cell fate choice determinant Numb, we show that asymmetric cell divisions take place in primary cultures of adult satellite cell derived myoblasts. We postulate that these events are also taking place in this lineage during embryonic and fœtal development and we are examining this phenomenon using various knock-in and transgenic tools. These genetically manipulated mice are also used to investigate how stem to differentiated cell transitions are regulated and how homeostasis is achieved in skeletal muscle.

More scientific information and projects… Publications since 2005

Kassar-Duchossoy, L., Giacone, E., Gayraud-Morel, B., Jory, A., Gomès, D., Tajbakhsh, S. (2005). Pax3/Pax7 mark a novel population of primitive myogenic cells during development. Genes & Dev. 3:1426-1431.

Tajbakhsh, S. (2005). Skeletal muscle stem and progenitor cells: Reconciling genetics and lineage. Exp Cell Res 306: 364-72.

Dufour, A., Shinin, V., Tajbakhsh, S., Guillen-Aghion, N., Olivo-Marin, J. C., and Zimmer, C. (2005). Segmenting and tracking fluorescent cells in dynamic 3-D microscopy with coupled active surfaces. IEEE Trans Image Process 14, 1396-410.

 Bajanca, F., M. Luz, K. Raymond, G.G. Martins, A. Sonnenberg, S. Tajbakhsh, M. Buckingham, and S. Thorsteinsdottir (2006). Integrin {alpha}6{beta}1-laminin interactions regulate early myotome formation in the mouse embryo. Development. 133:1635-44.

Relaix, F., D. Montarras, S. Zaffran, B. Gayraud-Morel, D. Rocancourt, S. Tajbakhsh, A. Mansouri, A. Cumano, and M. Buckingham (2006). Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells. J Cell Biol. 172:91-102.

 Shinin, V., Gayraud-Morel, B., Gomes, D., and Tajbakhsh, S. (2006). Asymmetric division and cosegregation of template DNA strands in adult muscle satellite cells. Nat Cell Biol 8, 677-82.

Biressi, S., E. Tagliafico, G. Lamorte, S. Monteverde, E. Tenedini, E. Roncaglia, S. Ferrari, M.G. Cusella-De Angelis, S. Tajbakhsh, and G. Cossu (2007). Intrinsic phenotypic diversity of embryonic and fetal myoblasts is revealed by genome-wide gene expression analysis on purified cells. Dev Biol. 304(2):633-51. Epub 2007 Jan. 12.

Christov, C., F. Chretien, R.A. Khalil, G. Bassez, G. Vallet, F.J. Authier, Y. Bassaglia, V. Shinin, S. Tajbakhsh, B. Chazaud, and R.K. Gherardi (2007). Muscle Satellite Cells and Endothelial Cells: Close Neighbors and Privileged Partners. Mol Biol Cell. 18(4):1397-409. Epub 2007 Feb 7.

Gayraud-Morel, B., F. Chrétien, P. Flamant, D. Gomès, P.S. Zammit, and S. Tajbakhsh (2007). A role for the myogenic determination gene Myf5 in adult regenerative myogenesis. Dev Biol. 312:13-28 Epub 2007 Sep 11.

Cossu G, Tajbakhsh S. (2007). Oriented cell divisions and muscle satellite cell heterogeneity. Cell 129(5):859-61.

 Jory, A., X. Cousin, and S. Tajbakhsh (2007). Formation du muscle, cellules souches, et régéneration musculaire. Biofutur 281: 37-40.

Sambasivan, R. and S. Tajbakhsh (2007). Skeletal muscle stem cell birth and properties. Semin Cell Dev Biol. 18: 870-882. Epub 2007 Oct 2.

Biressi S, Messina G, Collombat P, Tagliafico E, Monteverde S, Benedetti L, Cusella De Angelis MG, Mansouri A, Ferrari S, Tajbakhsh S, Broccoli V, Cossu G. (2008). The homeobox gene Arx is a novel positive regulator of embryonic myogenesis. Cell Death Differ. 15(1):94-104; Oct 12.

Rocheteau, P. and S. Tajbakhsh (2008). ADN Immortel ou signature épigénétique? Médecine/Sciences, 24: 847-852.

Tajbakhsh, S. (2008). Stem cell identity and template DNA strand segregation. Curr. Opin. Cell Biol. 20: 716-722.

Gayraud-Morel, B., F. Chrétien and S. Tajbakhsh (2009). Skeletal muscle as a paradigm for regenerative biology and medicine. Regenerative Medicine. 4:293-319.

Shinin, V. B. Gayraud-Morel and S. Tajbakhsh (2009). Template DNA strand cosegregation and asymmetric cell division in skeletal muscle stem cells. In: Stem Cells in Regenerative Medicine. Series: Methods in Molecular Biology (Humana Press, USA) 482: 295-317.

Sambasivan, R., B. Gayraud-Morel, G. Dumas, C. Cimper, S. Paisant, R. G. Kelly and S. Tajbakhsh (2009). Distinct regulatory cascades govern extraocular and pharyngeal arch muscle progenitor cell fates. Developmental Cell. 16: 810-821.

Shoji H, Deltour L, Nakamura T, Tajbakhsh S, Poirier F. (2009). Expression pattern and role of Galectin1 during early mouse myogenesis. Dev Growth Differ. Sep;51(7):607-15.

Castets P, Maugenre S, Gartioux C, Rederstorff M, Krol A, Lescure A, Tajbakhsh S, Allamand V, Guicheney P. (2009). Selenoprotein N is dynamically expressed during mouse development and detected early in muscle precursors. BMC Dev Biol.  Aug 22;9:46.

Tajbakhsh, S. (2009) Stem cell: what’s in a name? Nature Reports Stem Cells. June 25.

Jory, A., Le Roux, I., Gayraud-Morel, B., Rocheteau, Pierre, Cohen-Tannoudji, M., Cumano, A. and S. Tajbakhsh. (2009). Numb promotes progenitor cell self-renewal in the embryonic somite. Stem Cells  27: 2769-2780.

Tajbakhsh S. (2009). Skeletal muscle stem cells in developmental versus regenerative myogenesis. J Intern Med. 2009 Oct;266(4):372-89.

Tajbakhsh, S. Gonzales, C. (2009). Biased segregation of DNA and centrosomes: moving together or drifting apart? Nature Reviews Molecular & Cellular Biology 10: 804-810.

Tajbakhsh, S., Rocheteau, P., Le Roux, I. (2009) Asymmetric cell divisions and asymmetric cell fates. Annual Reviews in Cell & Developmental Biology. 25:671-99.

Tajbakhsh, S. Gonzales, C. (2009). Biased segregation of DNA and centrosomes: moving together or drifting apart? Nature Reviews Molecular & Cellular Biology 10: 804-810.

Theis S, Patel K, Valasek P, Otto A, Pu Q, Harel I, Tzahor E, Tajbakhsh S, Christ B, Huang R. (2010). The occipital lateral plate mesoderm is a novel source for vertebrate neck musculature. Development 137:2961-2971.

Sambasivan, R., Kuratani, S. and Tajbakhsh, S. (2011). An eye on the head: the development and evolution of craniofacial muscles. Development 138: 2401-15.
 
Sambasivan# R, Yao# R, Kissenpfennig A, Van Wittenberghe L, Paldi A, Gayraud-Morel B, Guenou H, Malissen B, Tajbakhsh S*, Galy A*. (2011). Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development 138: 3647-3656.
          # equal contributing authors; * co-corresponding authors
 
Tajbakhsh, S., G. Cavalli and E. Richet (2011). Integrated Gene Regulatory Circuits: Celebrating the 50th Anniversary of the Operon Model. Molecular Cell 43: 505-514.
 
Dellavalle, A., G. Maroli, D. Covarello, E. Azzoni1,, A. Innocenzi, L. Perani, S.Antonini, R. Sambasivan, S. Brunelli, S. Tajbakhsh and G. Cossu (2011). Pericytes resident in post-natal skeletal muscle differentiate into muscle fibers and enter the satellite cell pool. Nature Communications, 2:499.
 
Nowlan, N. C., Dumas, G., Tajbakhsh, S., Prendergast, P. J. and Murphy, P. (2012). Biophysical stimuli induced by passive movements compensate for lack of skeletal muscle during embryonic skeletogenesis. Biomech Model Mechanobiol, 11: 207-219.
 
P. Mourikis, R. Sambasivan, D. Castel, P. Rocheteau, V. Bizzarro and S. Tajbakhsh (2012). A critical requirement for Notch signaling in maintenance of the quiescent skeletal muscle stem cell state. Stem Cells, 30: 243-252.
 
Rocheteau, P., Gayraud-Morel, B., Siegl-Cachedenier, I., Blasco, M. and S. Tajbakhsh (2012). A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division. Cell, 48: 112-125.
 
B. Gayraud-Morel, F. Chrétien, A. Jory,R. Sambasivan, E. Negroni, P. Flamant, G. Soubigou, J.-Y. Coppée, J. Di Santo, A. Cumano, V. Mouly, and S. Tajbakhsh (2012).Haploinsufficiency of Myf5 reveals distinct cell fate potentials for adult skeletal muscle stem cells, J. Cell Science, in press.