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.
^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.
ISSN0092-8674.
PMID6091905.
S2CID28853102.
^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.
ISSN0028-0836.
PMID2552320.
S2CID4335995.
^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.
ISSN0950-1991.
PMID20823066.