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Head Muscles: Aliens Who Came in from the Cold?
Developmental Cell
Previews Head Muscles: Aliens Who Came in from the Cold? Anne C. Rios1 and Christophe Marcelle1,* 1Developmental Biology Institute of Marseille Luminy (IBDML), CNRS UMR 6216, Universite ´ de la Me´diterrane´e, Campus de Luminy, 13288 Marseille Cedex 09, France *Correspondence: [email protected] DOI 10.1016/j.devcel.2009.06.004
Two complementary studies by Harel et al. and Sambasivan et al. published in this issue of Developmental Cell show the overwhelming diversity in the developmental programs and embryonic origins of distinct muscle groups and their associated muscle stem cells. The head muscles are classified as follows: extraocular muscles (EOM), which move and rotate the eye in a coordinated manner; branchiomeric muscles, which control jaw movement, facial expression, and pharyngeal and laryngeal function; and finally, neck and tongue muscles (reviewed in Noden and Francis-West, 2006). A number of recently published analyses from various laboratories have shown that head muscles have adopted original molecular strategies for their differentiation. For instance, genetic evidence has shown parallels between cardiac and branchiomeric muscle developmental programs, which argue for the tissues’ common evolutionary origin (see Tzahor, 2009; Grifone and Kelly, 2007). At the same time, it has become clear that head muscles differ from their counterparts in the trunk and limbs. The first genetic evidence for this has come from the demonstration that, in Pax3:Myf5(Mrf4) mutants (where Mrf4 function is disrupted in cis), body muscles are absent, while they are present in the head (Tajbakhsh et al., 1997). Since this first report, evidence has been accumulating to indicate that muscle development is controlled by distinct factors in the head versus those of the rest of the body. Two complementary studies by Harel et al. (2009) and Sambasivan et al. (2009) published in this issue of Developmental Cell shed novel light on the surprising molecular diversity of distinct head muscle groups. Sambasivan and colleagues showed that—unlike all other skeletal muscles in the embryo, wherein MyoD can compensate for defective Myf5/Mrf4 function— EOM are entirely dependent on Myf5/ Mrf4 activity. Other muscles of the head, such as branchiomeric muscles, are not affected by the inactivation of these two genes. Conversely, in the branchiomeric
muscles, but not in the EOM, Tbx1 operates together with Myf5 upstream of Myod, much in the same way that Pax3 does in the body. Harel and colleagues addressed the question of head muscle diversity differently, genetically labeling the head muscles by crossing Myf5Cre, Pax3Cre, MesP1Cre, Isl1Cre, and Nkx2. 5Cre mouse lines with mouse EGFP and YFP lines (Z/EG and RosaYFP reporter lines). This analysis enabled them to draw a lineage map of the craniofacial anatomy, showing that distinct muscle groups (EOM, branchiomeric muscles, and tongue muscles) express different combinations of these markers, and therefore originate from distinct lineages. The data presented in these two papers are important because they show that skeletal muscle differentiation follows distinct molecular strategies in different parts of the body: although a core set of regulatory molecules (e.g., Pax7, Myf5, and Myod) is common to all muscles, complementary genetic pathways have been adopted in different anatomical locations, to assure self-renewal and the acquisition of cell fate (Figure 1). These findings may also provide a molecular framework to explain why certain myopathies are restricted to subsets of muscles. A second part of the work presented by the two groups addresses the embryonic origin and plasticity of head muscle stem cells, namely the satellite cells. Satellite cells are crucial mediators of muscle repair in adult animals. The embryological origin of satellite cells was first addressed over 25 years ago, in a chick-quail chimera study revealing that some satellite cells derive from the somites (Armand et al., 1983). However, these results did not rule out the possibilities that (1) some satellite cells were not derived from the grafted presomitic mesoderm (PSM) and
had a different embryonic origin, and (2) cells from a nonmuscle lineage, but derived from the grafted PSM tissue, may be the true origin of satellite cells. In particular, it was shown years later that early endothelial progenitors (i.e., hemangioblasts) arise from the PSM (Pardanaud et al., 1996) and can efficiently differentiate into muscle tissues if exposed to a proper environment (Cossu and Biressi, 2005). Harel et al. now determine that the embryonic origin of virtually all head satellite cells can be traced to the cranial paraxial mesoderm. Interestingly, they show that satellite cells maintain a close spatial relationship with the progenitors from which they are derived. They also adopted the inverse approach to make their point, genetically labeling the endothelial lineage from its earliest precursors (Zovein et al., 2008) to generate a mouse in which all endothelia are YFP labeled. They found no YFP-labeled satellite cells in the head or in the trunk, thereby ruling out an endothelial contribution to the satellite cell pool. These data reinforce recent experiments addressing the origin of satellite cells in the trunk, showing that satellite cells derive from a central region of the dermomyotome that gives rise to muscle and dermis, but not endothelia (Gros et al., 2005). However, these findings do not rule out the possibility that, in some pathological cases, cells from other sources can enter the satellite cell position, and participate to some extent in the regeneration of skeletal muscle fibers (Pe´ault et al., 2007). The last issue that is addressed by both groups is that of the plasticity of satellite cells. By using RT-PCR on satellite cells from different muscle groups of the head and the body, Sambasivan and Harel both show that cells from each muscle group display specific molecular
Developmental Cell 16, June 16, 2009 ª2009 Elsevier Inc. 779
Developmental Cell
Previews
Figure 1. Distinct Genetic Networks Regulate the Differentiation of Specific Muscle Groups in the Head and Trunk In each box are indicated the muscle group (light blue), their embryonic origin (green), specific transcription factors expressed by the embryonic lineage (purple), the cardiogenic potential of the relevant satellite cells (dark blue), and the genetic network regulating local muscle differentiation in the embryo (diagram). All satellite cells express a common core set of muscle-related factors (e.g., Myf5, MyoD, Pax7, and Met); other transcription factors reflect lineage-specific differences according to local origin (box, bottom right). Despite this, transplantation of satellite cells from head to trunk leads to their reprogramming, indicating a significant plasticity of adult head muscle stem cells. CPM: cranial paraxial mesoderm; SpM: slanchnic mesoderm; PM: prechordal mesoderm.
signatures characteristic of the specific factors important for the differentiation of the particular muscles from which they were isolated. However, these signatures are influenced by the local environment; they are lost when the satellite cells are transplanted to ectopic locations, or placed in culture in vitro. The molecular specificity of head satellite cells might nonetheless prove relevant for cell therapies to repair infarcted cardiac tissues. Harel and colleagues found that Isl1 lineage-derived satellite cells from branchiomeric muscles (which share a common embryonic origin with myocardial and endocardial cell populations arising from the splanchnic mesoderm) may retain cardiogenic potential that satellite cells from other sources do not display. Satellite cells from head muscles
could therefore provide a source of cells to repair cardiac damage (Figure 1), an exercise at which satellite cells from trunk muscles perform very poorly. These studies may provide a framework to address the etiology of various myopathic diseases that differentially affect various muscles in patients. REFERENCES Armand, O., Boutineau, A.M., Mauger, A., Pautou, M.P., and Kieny, M. (1983). Arch. Anat. Microsc. Morphol. Exp. 72, 163–181. Cossu, G., and Biressi, S. (2005). Semin. Cell Dev. Biol. 16, 623–631.
Harel, I., Nathan, E., Tirosh-Finkel, L., Zigdon, H., Guimara˜es-Camboa, N., Evans, S.M., and Tzahor, E. (2009). Dev. Cell 16, this issue, 822–832. Noden, D.M., and Francis-West, P. (2006). Dev. Dyn. 235, 1194–1218. Pardanaud, L., Luton, D., Prigent, M., Bourcheix, L.M., Catala, M., and Dieterlen-Lievre, F. (1996). Development 122, 1363–1371. Pe´ault, B., Rudnicki, M., Torrente, Y., Cossu, G., Tremblay, J.P., Partridge, T., Gussoni, E., Kunkel, L.M., and Huard, J. (2007). Mol. Ther. 15, 867–877. Sambasivan, R., Gayraud-Morel, B., Dumas, G., Cimper, C., Paisant, S., Kelly, R., and Tajbakhsh, S. (2009). Dev. Cell 16, this issue, 810–821. Tajbakhsh, S., Rocancourt, D., Cossu, G., and Buckingham, M. (1997). Cell 89, 127–138. Tzahor, E. (2009). Dev. Biol. 327, 273–279.
Grifone, R., and Kelly, R.G. (2007). Trends Genet. 23, 365–369. Gros, J., Manceau, M., Thome´, V., and Marcelle, C. (2005). Nature 435, 954–958.
780 Developmental Cell 16, June 16, 2009 ª2009 Elsevier Inc.
Zovein, A.C., Hofmann, J.J., Lynch, M., French, W.J., Turlo, K.A., Yang, Y., Becker, M.S., Zanetta, L., Dejana, E., Gasson, J.C., et al. (2008). Cell Stem Cell 3, 625–636.
Previews Head Muscles: Aliens Who Came in from the Cold? Anne C. Rios1 and Christophe Marcelle1,* 1Developmental Biology Institute of Marseille Luminy (IBDML), CNRS UMR 6216, Universite ´ de la Me´diterrane´e, Campus de Luminy, 13288 Marseille Cedex 09, France *Correspondence: [email protected] DOI 10.1016/j.devcel.2009.06.004
Two complementary studies by Harel et al. and Sambasivan et al. published in this issue of Developmental Cell show the overwhelming diversity in the developmental programs and embryonic origins of distinct muscle groups and their associated muscle stem cells. The head muscles are classified as follows: extraocular muscles (EOM), which move and rotate the eye in a coordinated manner; branchiomeric muscles, which control jaw movement, facial expression, and pharyngeal and laryngeal function; and finally, neck and tongue muscles (reviewed in Noden and Francis-West, 2006). A number of recently published analyses from various laboratories have shown that head muscles have adopted original molecular strategies for their differentiation. For instance, genetic evidence has shown parallels between cardiac and branchiomeric muscle developmental programs, which argue for the tissues’ common evolutionary origin (see Tzahor, 2009; Grifone and Kelly, 2007). At the same time, it has become clear that head muscles differ from their counterparts in the trunk and limbs. The first genetic evidence for this has come from the demonstration that, in Pax3:Myf5(Mrf4) mutants (where Mrf4 function is disrupted in cis), body muscles are absent, while they are present in the head (Tajbakhsh et al., 1997). Since this first report, evidence has been accumulating to indicate that muscle development is controlled by distinct factors in the head versus those of the rest of the body. Two complementary studies by Harel et al. (2009) and Sambasivan et al. (2009) published in this issue of Developmental Cell shed novel light on the surprising molecular diversity of distinct head muscle groups. Sambasivan and colleagues showed that—unlike all other skeletal muscles in the embryo, wherein MyoD can compensate for defective Myf5/Mrf4 function— EOM are entirely dependent on Myf5/ Mrf4 activity. Other muscles of the head, such as branchiomeric muscles, are not affected by the inactivation of these two genes. Conversely, in the branchiomeric
muscles, but not in the EOM, Tbx1 operates together with Myf5 upstream of Myod, much in the same way that Pax3 does in the body. Harel and colleagues addressed the question of head muscle diversity differently, genetically labeling the head muscles by crossing Myf5Cre, Pax3Cre, MesP1Cre, Isl1Cre, and Nkx2. 5Cre mouse lines with mouse EGFP and YFP lines (Z/EG and RosaYFP reporter lines). This analysis enabled them to draw a lineage map of the craniofacial anatomy, showing that distinct muscle groups (EOM, branchiomeric muscles, and tongue muscles) express different combinations of these markers, and therefore originate from distinct lineages. The data presented in these two papers are important because they show that skeletal muscle differentiation follows distinct molecular strategies in different parts of the body: although a core set of regulatory molecules (e.g., Pax7, Myf5, and Myod) is common to all muscles, complementary genetic pathways have been adopted in different anatomical locations, to assure self-renewal and the acquisition of cell fate (Figure 1). These findings may also provide a molecular framework to explain why certain myopathies are restricted to subsets of muscles. A second part of the work presented by the two groups addresses the embryonic origin and plasticity of head muscle stem cells, namely the satellite cells. Satellite cells are crucial mediators of muscle repair in adult animals. The embryological origin of satellite cells was first addressed over 25 years ago, in a chick-quail chimera study revealing that some satellite cells derive from the somites (Armand et al., 1983). However, these results did not rule out the possibilities that (1) some satellite cells were not derived from the grafted presomitic mesoderm (PSM) and
had a different embryonic origin, and (2) cells from a nonmuscle lineage, but derived from the grafted PSM tissue, may be the true origin of satellite cells. In particular, it was shown years later that early endothelial progenitors (i.e., hemangioblasts) arise from the PSM (Pardanaud et al., 1996) and can efficiently differentiate into muscle tissues if exposed to a proper environment (Cossu and Biressi, 2005). Harel et al. now determine that the embryonic origin of virtually all head satellite cells can be traced to the cranial paraxial mesoderm. Interestingly, they show that satellite cells maintain a close spatial relationship with the progenitors from which they are derived. They also adopted the inverse approach to make their point, genetically labeling the endothelial lineage from its earliest precursors (Zovein et al., 2008) to generate a mouse in which all endothelia are YFP labeled. They found no YFP-labeled satellite cells in the head or in the trunk, thereby ruling out an endothelial contribution to the satellite cell pool. These data reinforce recent experiments addressing the origin of satellite cells in the trunk, showing that satellite cells derive from a central region of the dermomyotome that gives rise to muscle and dermis, but not endothelia (Gros et al., 2005). However, these findings do not rule out the possibility that, in some pathological cases, cells from other sources can enter the satellite cell position, and participate to some extent in the regeneration of skeletal muscle fibers (Pe´ault et al., 2007). The last issue that is addressed by both groups is that of the plasticity of satellite cells. By using RT-PCR on satellite cells from different muscle groups of the head and the body, Sambasivan and Harel both show that cells from each muscle group display specific molecular
Developmental Cell 16, June 16, 2009 ª2009 Elsevier Inc. 779
Developmental Cell
Previews
Figure 1. Distinct Genetic Networks Regulate the Differentiation of Specific Muscle Groups in the Head and Trunk In each box are indicated the muscle group (light blue), their embryonic origin (green), specific transcription factors expressed by the embryonic lineage (purple), the cardiogenic potential of the relevant satellite cells (dark blue), and the genetic network regulating local muscle differentiation in the embryo (diagram). All satellite cells express a common core set of muscle-related factors (e.g., Myf5, MyoD, Pax7, and Met); other transcription factors reflect lineage-specific differences according to local origin (box, bottom right). Despite this, transplantation of satellite cells from head to trunk leads to their reprogramming, indicating a significant plasticity of adult head muscle stem cells. CPM: cranial paraxial mesoderm; SpM: slanchnic mesoderm; PM: prechordal mesoderm.
signatures characteristic of the specific factors important for the differentiation of the particular muscles from which they were isolated. However, these signatures are influenced by the local environment; they are lost when the satellite cells are transplanted to ectopic locations, or placed in culture in vitro. The molecular specificity of head satellite cells might nonetheless prove relevant for cell therapies to repair infarcted cardiac tissues. Harel and colleagues found that Isl1 lineage-derived satellite cells from branchiomeric muscles (which share a common embryonic origin with myocardial and endocardial cell populations arising from the splanchnic mesoderm) may retain cardiogenic potential that satellite cells from other sources do not display. Satellite cells from head muscles
could therefore provide a source of cells to repair cardiac damage (Figure 1), an exercise at which satellite cells from trunk muscles perform very poorly. These studies may provide a framework to address the etiology of various myopathic diseases that differentially affect various muscles in patients. REFERENCES Armand, O., Boutineau, A.M., Mauger, A., Pautou, M.P., and Kieny, M. (1983). Arch. Anat. Microsc. Morphol. Exp. 72, 163–181. Cossu, G., and Biressi, S. (2005). Semin. Cell Dev. Biol. 16, 623–631.
Harel, I., Nathan, E., Tirosh-Finkel, L., Zigdon, H., Guimara˜es-Camboa, N., Evans, S.M., and Tzahor, E. (2009). Dev. Cell 16, this issue, 822–832. Noden, D.M., and Francis-West, P. (2006). Dev. Dyn. 235, 1194–1218. Pardanaud, L., Luton, D., Prigent, M., Bourcheix, L.M., Catala, M., and Dieterlen-Lievre, F. (1996). Development 122, 1363–1371. Pe´ault, B., Rudnicki, M., Torrente, Y., Cossu, G., Tremblay, J.P., Partridge, T., Gussoni, E., Kunkel, L.M., and Huard, J. (2007). Mol. Ther. 15, 867–877. Sambasivan, R., Gayraud-Morel, B., Dumas, G., Cimper, C., Paisant, S., Kelly, R., and Tajbakhsh, S. (2009). Dev. Cell 16, this issue, 810–821. Tajbakhsh, S., Rocancourt, D., Cossu, G., and Buckingham, M. (1997). Cell 89, 127–138. Tzahor, E. (2009). Dev. Biol. 327, 273–279.
Grifone, R., and Kelly, R.G. (2007). Trends Genet. 23, 365–369. Gros, J., Manceau, M., Thome´, V., and Marcelle, C. (2005). Nature 435, 954–958.
780 Developmental Cell 16, June 16, 2009 ª2009 Elsevier Inc.
Zovein, A.C., Hofmann, J.J., Lynch, M., French, W.J., Turlo, K.A., Yang, Y., Becker, M.S., Zanetta, L., Dejana, E., Gasson, J.C., et al. (2008). Cell Stem Cell 3, 625–636.