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Six Homeoproteins Directly Activate Myod Expression in the Gene Regulatory Networks That Control Early Myogenesis: e1003425

In mammals, several genetic pathways have been characterized that govern engagement of multipotent embryonic progenitors into the myogenic program through the control of the key myogenic regulatory gene Myod. Here we demonstrate the involvement of Six homeoproteins. We first targeted into a Pax3 all...

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Published in:PLoS genetics 2013-04, Vol.9 (4)
Main Authors: Relaix, Frédéric, Demignon, Josiane, Laclef, Christine, Pujol, Julien, Santolini, Marc, Niro, Claire, Lagha, Mounia, Rocancourt, Didier, Buckingham, Margaret, Maire, Pascal
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container_title PLoS genetics
container_volume 9
creator Relaix, Frédéric
Demignon, Josiane
Laclef, Christine
Pujol, Julien
Santolini, Marc
Niro, Claire
Lagha, Mounia
Rocancourt, Didier
Buckingham, Margaret
Maire, Pascal
description In mammals, several genetic pathways have been characterized that govern engagement of multipotent embryonic progenitors into the myogenic program through the control of the key myogenic regulatory gene Myod. Here we demonstrate the involvement of Six homeoproteins. We first targeted into a Pax3 allele a sequence encoding a negative form of Six4 that binds DNA but cannot interact with essential Eya co-factors. The resulting embryos present hypoplasic skeletal muscles and impaired Myod activation in the trunk in the absence of Myf5/Mrf4. At the axial level, we further show that Myod is still expressed in compound Six1/Six4:Pax3 but not in Six1/Six4:Myf5 triple mutant embryos, demonstrating that Six1/4 participates in the Pax3-Myod genetic pathway. Myod expression and head myogenesis is preserved in Six1/Six4:Myf5 triple mutant embryos, illustrating that upstream regulators of Myod in different embryonic territories are distinct. We show that Myod regulatory regions are directly controlled by Six proteins and that, in the absence of Six1 and Six4, Six2 can compensate.
doi_str_mv 10.1371/journal.pgen.1003425
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subjects Cell culture
Deoxyribonucleic acid
DNA
Experiments
Genes
Genetic engineering
Insects
Proteins
Rodents
title Six Homeoproteins Directly Activate Myod Expression in the Gene Regulatory Networks That Control Early Myogenesis: e1003425
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