Margaret Buckingham

Last updated
Margaret Buckingham
ForMemRS
Born (1945-03-02) 2 March 1945 (age 79)
UK
Citizenshipdual French-British
Alma mater Lady Margaret Hall, Oxford [1]
Website https://www.pasteur.fr/en/developmental-and-stem-cell-biology

Margaret Buckingham, ForMemRS (born 2 March 1945) is a British developmental biologist working in the fields of myogenesis and cardiogenesis. She is an honorary professor at the Pasteur Institute in Paris and emeritus director in the Centre national de la recherche scientifique (CNRS). [2] She is a member of the European Molecular Biology Organization, the Academia Europaea and the French Academy of Sciences.

Contents

Biography

Margaret Buckingham was educated in Scotland and at Oxford University where she obtained B.A., M.A. and D.Phil. degrees in Biochemistry. As a postdoc, she then joined François Gros at the Pasteur Institute in Paris where she subsequently pursued her scientific career. She is an honorary professor at the Pasteur Institute and emeritus director in the Centre national de la recherche scientifique (CNRS). She is a member of the scientific council of the ERC [3] and chairs the prize committee of the Lefoulon-Delalande Foundation for cardiovascular research. In 2013, she was awarded the gold medal of the CNRS. [4] [5] She is a member of the French Academy of sciences, [6] a foreign/honorary member of the Royal Society of London/Edinburgh and a foreign associate of the National Academy of Sciences of the USA. She is also a member of EMBO and of the Academia Europaea. [7] [ circular reference ] She has French and British nationality, and is married to Richard Buckingham, Editor-in-Chief of Biochimie until December 2020, with three children.

Scientific research

Margaret Buckingham is a developmental biologist who is interested in how naïve multipotent cells acquire tissue specificity during embryogenesis. She has studied both the formation of skeletal muscle and of the heart, using the tools of mouse molecular genetics to characterise cell behaviour and to identify the genes that govern cell fate choices.

From pioneering research on the in vivo expression, structure and regulation of muscle genes, [8] she and her lab went on to study the myogenic regulatory factors, [9] showing that Myf5 is present before MyoD in the embryo and that in the absence of Myf5 and Mrf4, cells fail to form skeletal muscle and acquire other mesodermal cell fates. [10] Characterisation of Myf5 enhancers revealed a direct role for Pax3 in their transcriptional activation at different sites of myogenesis. [11] From genetic screens, they identified other Pax3 targets, demonstrating the central role of Pax3 in the gene regulatory network that leads to the onset of myogenesis in the embryo. [12] [13] They discovered a population of Pax3/Pax7-positive progenitors that are essential for foetal muscle development [14] and showed that Pax-positive satellite cells associated with adult fibres constitute stem cells for muscle regeneration. [15] They identified genes, including Pitx2/3, that affect the behaviour of these cells and showed that Myf5 mRNA, present in quiescent satellite cells is sequestered until these cells are activated after injury. [16]

Her main contribution to cardiogenesis is the identification of the second heart field (SHF) as a major source of cardiac progenitor cells that form specific regions of the heart. [17] [18] The behaviour of these cells is controlled by gene regulatory networks and signalling pathways, exemplified by the FGF10 gene. [19] Retrospective clonal analysis complemented their work on the SHF and established a lineage tree for the myocardium, where the second lineage defines the SHF contribution whereas the first lineage contributes all the left ventricular myocardium. [20] This analysis revealed the clonal relationships between different sublineages that contribute to both cardiac muscle at the poles of the heart and anterior skeletal muscles [13] [21] which are not under Pax3-control. [13] [22] In addition to its conceptual importance for cardiogenesis, this work also has biomedical implications for congenital heart malformations.

Awards and honours

Amsen, Eva (2011-01-25). "An interview with Margaret Buckingham: President of the French Society of Developmental Biology". Development . 138 (4). The Company of Biologists Ltd: 599–600. doi: 10.1242/dev.060228 . PMID   21266403.

Related Research Articles

<span class="mw-page-title-main">Muscle cell</span> Type of cell found in muscle tissue

A muscle cell, also known as a myocyte, is a mature contractile cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal, smooth, and cardiac (cardiomyocytes). A skeletal muscle cell is long and threadlike with many nuclei and is called a muscle fiber. Muscle cells develop from embryonic precursor cells called myoblasts.

G<sub>0</sub> phase Quiescent stage of the cell cycle in which the cell does not divide

The G0 phase describes a cellular state outside of the replicative cell cycle. Classically, cells were thought to enter G0 primarily due to environmental factors, like nutrient deprivation, that limited the resources necessary for proliferation. Thus it was thought of as a resting phase. G0 is now known to take different forms and occur for multiple reasons. For example, most adult neuronal cells, among the most metabolically active cells in the body, are fully differentiated and reside in a terminal G0 phase. Neurons reside in this state, not because of stochastic or limited nutrient supply, but as a part of their developmental program.

<span class="mw-page-title-main">MyoD</span> Mammalian protein found in Homo sapiens

MyoD, also known as myoblast determination protein 1, is a protein in animals that plays a major role in regulating muscle differentiation. MyoD, which was discovered in the laboratory of Harold M. Weintraub, belongs to a family of proteins known as myogenic regulatory factors (MRFs). These bHLH transcription factors act sequentially in myogenic differentiation. Vertebrate MRF family members include MyoD1, Myf5, myogenin, and MRF4 (Myf6). In non-vertebrate animals, a single MyoD protein is typically found.

Myosatellite cells, also known as satellite cells, muscle stem cells or MuSCs, are small multipotent cells with very little cytoplasm found in mature muscle. Satellite cells are precursors to skeletal muscle cells, able to give rise to satellite cells or differentiated skeletal muscle cells. They have the potential to provide additional myonuclei to their parent muscle fiber, or return to a quiescent state. More specifically, upon activation, satellite cells can re-enter the cell cycle to proliferate and differentiate into myoblasts.

<span class="mw-page-title-main">Pax genes</span> Family of transcription factors

In evolutionary developmental biology, Paired box (Pax) genes are a family of genes coding for tissue specific transcription factors containing an N-terminal paired domain and usually a partial, or in the case of four family members, a complete homeodomain to the C-terminus. An octapeptide as well as a Pro-Ser-Thr-rich C terminus may also be present. Pax proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such.

<span class="mw-page-title-main">PAX3</span> Paired box gene 3

The PAX3 gene encodes a member of the paired box or PAX family of transcription factors. The PAX family consists of nine human (PAX1-PAX9) and nine mouse (Pax1-Pax9) members arranged into four subfamilies. Human PAX3 and mouse Pax3 are present in a subfamily along with the highly homologous human PAX7 and mouse Pax7 genes. The human PAX3 gene is located in the 2q36.1 chromosomal region, and contains 10 exons within a 100 kb region.

<span class="mw-page-title-main">Myogenesis</span> Formation of muscular tissue, particularly during embryonic development

Myogenesis is the formation of skeletal muscular tissue, particularly during embryonic development.

<span class="mw-page-title-main">Myogenin</span> Mammalian protein found in Homo sapiens

Myogenin, is a transcriptional activator encoded by the MYOG gene. Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is a member of the MyoD family of transcription factors, which also includes MyoD, Myf5, and MRF4.

<span class="mw-page-title-main">GDF11</span> Protein-coding gene in humans

Growth differentiation factor 11 (GDF11), also known as bone morphogenetic protein 11 (BMP-11), is a protein that in humans is encoded by the growth differentiation factor 11 gene. GDF11 is a member of the Transforming growth factor beta family.

<span class="mw-page-title-main">Muscle</span> Basic biological tissue

Muscle is a soft tissue, one of the four basic types of animal tissue. Muscle tissue gives skeletal muscles the ability to contract. Muscle is formed during embryonic development, in a process known as myogenesis. Muscle tissue contains special contractile proteins called actin and myosin which interact to cause movement. Among many other muscle proteins, present are two regulatory proteins, troponin and tropomyosin.

<span class="mw-page-title-main">PITX2</span> Protein-coding gene in the species Homo sapiens

Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.

<span class="mw-page-title-main">Integrin alpha 7</span>

Alpha-7 integrin is a protein that in humans is encoded by the ITGA7 gene. Alpha-7 integrin is critical for modulating cell-matrix interactions. Alpha-7 integrin is highly expressed in cardiac muscle, skeletal muscle and smooth muscle cells, and localizes to Z-disc and costamere structures. Mutations in ITGA7 have been associated with congenital myopathies and noncompaction cardiomyopathy, and altered expression levels of alpha-7 integrin have been identified in various forms of muscular dystrophy.

<span class="mw-page-title-main">CDH15</span> Protein-coding gene in humans

Cadherin-15 is a protein that in humans is encoded by the CDH15 gene.

<span class="mw-page-title-main">NEO1</span> Protein-coding gene in the species Homo sapiens

Neogenin is a protein that in humans is encoded by the NEO1 gene.

<span class="mw-page-title-main">MEOX1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein MOX-1 is a protein that in humans is encoded by the MEOX1 gene.

Wingless-type MMTV integration site family, member 6, also known as WNT6, is a human gene.

<span class="mw-page-title-main">C2C12</span> Mouse myoblast cell line

C2C12 is an immortalized mouse myoblast cell line. The C2C12 cell line is a subclone of myoblasts that were originally obtained by Yaffe and Saxel at the Weizmann Institute of Science in Israel in 1977. Developed for in vitro studies of myoblasts isolated from the complex interactions of in vivo conditions, C2C12 cells are useful in biomedical research. These cells are capable of rapid proliferation under high serum conditions and differentiation into myotubes under low serum conditions. Mononucleated myoblasts can later fuse to form multinucleated myotubes under low serum conditions or starvation, leading to the precursors of contractile skeletal muscle cells in the process of myogenesis. C2C12 cells are used to study the differentiation of myoblasts, osteoblasts, and myogenesis, to express various target proteins, and to explore mechanistic biochemical pathways.

<span class="mw-page-title-main">P19 cell</span>

P19 cells is an embryonic carcinoma cell line derived from an embryo-derived teratocarcinoma in mice. The cell line is pluripotent and can differentiate into cell types of all three germ layers. Also, it is the most characterized embryonic carcinoma (EC) cell line that can be induced into cardiac muscle cells and neuronal cells by different specific treatments. Indeed, exposing aggregated P19 cells to dimethyl sulfoxide (DMSO) induces differentiation into cardiac and skeletal muscle. Also, exposing P19 cells to retinoic acid (RA) can differentiate them into neuronal cells.

<span class="mw-page-title-main">MYF5</span> Protein-coding gene in the species Homo sapiens

Myogenic factor 5 is a protein that in humans is encoded by the MYF5 gene. It is a protein with a key role in regulating muscle differentiation or myogenesis, specifically the development of skeletal muscle. Myf5 belongs to a family of proteins known as myogenic regulatory factors (MRFs). These basic helix loop helix transcription factors act sequentially in myogenic differentiation. MRF family members include Myf5, MyoD (Myf3), myogenin, and MRF4 (Myf6). This transcription factor is the earliest of all MRFs to be expressed in the embryo, where it is only markedly expressed for a few days. It functions during that time to commit myogenic precursor cells to become skeletal muscle. In fact, its expression in proliferating myoblasts has led to its classification as a determination factor. Furthermore, Myf5 is a master regulator of muscle development, possessing the ability to induce a muscle phenotype upon its forced expression in fibroblastic cells.

<span class="mw-page-title-main">MYF6</span> Protein-coding gene in the species Homo sapiens

Myogenic factor 6 is a protein that in humans is encoded by the MYF6 gene. This gene is also known in the biomedical literature as MRF4 and herculin. MYF6 is a myogenic regulatory factor (MRF) involved in the process known as myogenesis.

References

  1. ↑ "Prominent alumni". Lady Margaret Hall, Oxford. Retrieved 30 November 2020.
  2. ↑ "Developmental biologist Margaret Buckingham is awarded the 2013 CNRS Gold Medal". Consulate General of France in Vancouver. Retrieved 4 November 2013.
  3. ↑ "ERC".
  4. ↑ Communiqué de presse du CNRS publié le 18 septembre 2013.
  5. ↑ "Article La Croix, Médaille d'or du CNRS". La Croix. 18 September 2013.
  6. ↑ "Académie des sciences".
  7. ↑ "Academia europaea".
  8. ↑ Robert, Benoît; Daubas, Philippe; Akimenko, Marie-Andrée; Cohen, Arlette; Garner, Ian; Guenet, Jean-Louis; Buckingham, Margaret (November 1984). "A single locus in the mouse encodes both myosin light chains 1 and 3, a second locus corresponds to a related pseudogene". Cell. 39 (1): 129–140. doi:10.1016/0092-8674(84)90198-3. ISSN   0092-8674. PMID   6091905. S2CID   28853102.
  9. ↑ Sassoon, David; Lyons, Gary; Wright, Woodring E.; Lin, Victor; Lassar, Andrew; Weintraub, Harold; Buckingham, Margaret (September 1989). "Expression of two myogenic regulatory factors myogenin and MyoDl during mouse embryogenesis". Nature. 341 (6240): 303–307. Bibcode:1989Natur.341..303S. doi:10.1038/341303a0. ISSN   0028-0836. PMID   2552320. S2CID   4335995.
  10. ↑ Tajbakhsh, S.; Rocancourt, D.; Buckingham, M. (November 1996). "Muscle progenitor cells failing to respond to positional cues adopt non-myogenic fates in myf-5 null mice". Nature. 384 (6606): 266–270. Bibcode:1996Natur.384..266T. doi:10.1038/384266a0. ISSN   0028-0836. PMID   8918877. S2CID   4337095.
  11. ↑ Bajard, L. (2006-09-01). "A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly activates Myf5 in muscle progenitor cells in the limb". Genes & Development. 20 (17): 2450–2464. doi:10.1101/gad.382806. ISSN   0890-9369. PMC   1560418 . PMID   16951257.
  12. ↑ Lagha, Mounia; Brunelli, Silvia; Messina, Graziella; Cumano, Ana; Kume, Tsutomu; Relaix, Frédéric; Buckingham, Margaret E. (December 2009). "Pax3:Foxc2 Reciprocal Repression in the Somite Modulates Muscular versus Vascular Cell Fate Choice in Multipotent Progenitors". Developmental Cell. 17 (6): 892–899. doi: 10.1016/j.devcel.2009.10.021 . ISSN   1534-5807. PMID   20059958.
  13. 1 2 3 Buckingham, Margaret (2017-06-05). "Gene regulatory networks and cell lineages that underlie the formation of skeletal muscle". Proceedings of the National Academy of Sciences. 114 (23): 5830–5837. Bibcode:2017PNAS..114.5830B. doi: 10.1073/pnas.1610605114 . ISSN   0027-8424. PMC   5468682 . PMID   28584083.
  14. ↑ Relaix, Frédéric; Rocancourt, Didier; Mansouri, Ahmed; Buckingham, Margaret (2005-04-20). "A Pax3/Pax7-dependent population of skeletal muscle progenitor cells". Nature. 435 (7044): 948–953. Bibcode:2005Natur.435..948R. doi:10.1038/nature03594. hdl: 11858/00-001M-0000-0012-E8E0-9 . ISSN   0028-0836. PMID   15843801. S2CID   4415583.
  15. ↑ Montarras, D. (2005-09-23). "Direct Isolation of Satellite Cells for Skeletal Muscle Regeneration". Science. 309 (5743): 2064–2067. Bibcode:2005Sci...309.2064M. doi: 10.1126/science.1114758 . ISSN   0036-8075. PMID   16141372. S2CID   39333234.
  16. ↑ Crist, Colin G.; Montarras, Didier; Buckingham, Margaret (July 2012). "Muscle Satellite Cells Are Primed for Myogenesis but Maintain Quiescence with Sequestration of Myf5 mRNA Targeted by microRNA-31 in mRNP Granules". Cell Stem Cell. 11 (1): 118–126. doi: 10.1016/j.stem.2012.03.011 . ISSN   1934-5909. PMID   22770245.
  17. ↑ Kelly, Robert G.; Brown, Nigel A.; Buckingham, Margaret E. (September 2001). "The Arterial Pole of the Mouse Heart Forms from Fgf10-Expressing Cells in Pharyngeal Mesoderm". Developmental Cell. 1 (3): 435–440. doi: 10.1016/s1534-5807(01)00040-5 . ISSN   1534-5807. PMID   11702954.
  18. ↑ Buckingham, Margaret; Meilhac, Sigolène; Zaffran, Stéphane (November 2005). "Building the mammalian heart from two sources of myocardial cells". Nature Reviews Genetics. 6 (11): 826–835. doi:10.1038/nrg1710. ISSN   1471-0056. PMID   16304598. S2CID   28455128.
  19. ↑ Watanabe, Y.; Zaffran, S.; Kuroiwa, A.; Higuchi, H.; Ogura, T.; Harvey, R. P.; Kelly, R. G.; Buckingham, M. (2012-10-23). "Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium". Proceedings of the National Academy of Sciences. 109 (45): 18273–18280. doi: 10.1073/pnas.1215360109 . ISSN   0027-8424. PMC   3494960 . PMID   23093675.
  20. ↑ Meilhac, Sigolène M; Esner, Milan; Kelly, Robert G; Nicolas, Jean-François; Buckingham, Margaret E (May 2004). "The Clonal Origin of Myocardial Cells in Different Regions of the Embryonic Mouse Heart" (PDF). Developmental Cell. 6 (5): 685–698. doi:10.1016/s1534-5807(04)00133-9. ISSN   1534-5807. PMID   15130493. S2CID   25041610.
  21. ↑ Lescroart, F.; Kelly, R. G.; Le Garrec, J.-F.; Nicolas, J.-F.; Meilhac, S. M.; Buckingham, M. (2010-09-07). "Clonal analysis reveals common lineage relationships between head muscles and second heart field derivatives in the mouse embryo". Development. 137 (19): 3269–3279. doi:10.1242/dev.050674. ISSN   0950-1991. PMID   20823066.
  22. ↑ Tajbakhsh, Shahragim; Rocancourt, Didier; Cossu, Giulio; Buckingham, Margaret (April 1997). "Redefining the Genetic Hierarchies Controlling Skeletal Myogenesis: Pax-3 and Myf-5 Act Upstream of MyoD". Cell. 89 (1): 127–138. doi: 10.1016/s0092-8674(00)80189-0 . ISSN   0092-8674. PMID   9094721. S2CID   18747744.
  23. ↑ "Professor Margaret Elizabeth Buckingham FRS, HonFRSE". The Royal Society of Edinburgh. Retrieved 9 February 2018.
  24. ↑ ARTIFICA (18 September 2013). "Developmental biologist Margaret Buckingham is awarded the 2013 CNRS Gold Medal". CNRS (in French). Retrieved 3 November 2017.
  25. ↑ CNRS (1999). "Les quinze lauréats de la Médaille d'argent du CNRS 1999". cnrs.fr. Archived from the original on 22 February 2014. Retrieved 21 February 2014.
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