Hox Proteins Display a Common and Ancestral Ability to Diversify Their Interaction Mode with the PBC Class Cofactors

Hox protein function during development and evolution relies on conserved multiple interaction modes with cofactors of the PBC and Meis families

Etude des facteurs myogéniques Myf5 et MyoD au cours du développement embryonnaire chez le poulet

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Delta 1-activated Notch inhibits muscle differentiation without affecting <i>Myf5</i> and <i>Pax3</i> expression in chick limb myogenesis

ABSTRACT The myogenic basic helix-loop-helix (bHLH) transcription factors, Myf5, MyoD, myogenin and MRF4, are unique in their ability to direct a program of specific gene transcription leading to skeletal muscle phenotype. The observation that Myf5 and MyoD can force myogenic conversion in non-muscle cells in vitro does not imply that they are equivalent. In this paper, we show that Myf5 transcripts are detected before those of MyoD during chick limb development. The Myf5 expression domain resembles that of Pax3 and is larger than that of MyoD. Moreover, Myf5 and Pax3 expression is correlated with myoblast proliferation, while MyoD is detected in post-mitotic myoblasts. These data indicate that Myf5 and MyoD are involved in different steps during chick limb bud myogenesis, Myf5 acting upstream of MyoD. The progression of myoblasts through the differentiation steps must be carefully controlled to ensure myogenesis at the right place and time during wing development. Because Notch signalling is known to prevent differentiation in different systems and species, we sought to determine whether these molecules regulate the steps occurring during chick limb myogenesis. Notch1 transcripts are associated with immature myoblasts, while cells expressing the ligands Delta1 and Serrate2 are more advanced in myogenesis. Misexpression of Delta1 using a replication-competent retrovirus activates the Notch pathway. After activation of this pathway, myoblasts still express Myf5 and Pax3 but have downregulated MyoD, resulting in inhibition of terminal muscle differentiation. We conclude that activation of Notch signalling during chick limb myogenesis prevents Myf5-expressing myoblasts from progressing to the MyoD-expressing stage.</jats:p

Delta 1-activated Notch inhibits muscle differentiation without affecting Myf5 and Pax3 expression in chick limb myogenesis

International audienceThe myogenic basic helix-loop-helix (bHLH) transcription factors, Myf5, MyoD, myogenin and MRF4, are unique in their ability to direct a program of specific gene transcription leading to skeletal muscle phenotype. The observation that Myf5 and MyoD can force myogenic conversion in non-muscle cells in vitro does not imply that they are equivalent. In this paper, we show that Myf5 transcripts are detected before those of MyoD during chick limb development. The Myf5 expression domain resembles that of Pax3 and is larger than that of MyoD. Moreover, Myf5 and Pax3 expression is correlated with myoblast proliferation, while MyoD is detected in post-mitotic myoblasts. These data indicate that Myf5 and MyoD are involved in different steps during chick limb bud myogenesis, Myf5 acting upstream of MyoD. The progression of myoblasts through the differentiation steps must be carefully controlled to ensure myogenesis at the right place and time during wing development. Because Notch signalling is known to prevent differentiation in different systems and species, we sought to determine whether these molecules regulate the steps occurring during chick limb myogenesis. Notch1 transcripts are associated with immature myoblasts, while cells expressing the ligands Delta1 and Serrate2 are more advanced in myogenesis. Misexpression of Delta1 using a replication-competent retrovirus activates the Notch pathway. After activation of this pathway, myoblasts still express Myf5 and Pax3 but have downregulated MyoD, resulting in inhibition of terminal muscle differentiation. We conclude that activation of Notch signalling during chick limb myogenesis prevents Myf5-expressing myoblasts from progressing to the MyoD-expressing stag

The Generic Facet of Hox Protein Function

International audienc

HOXB8 counteracts MAPK/ERK oncogenic signaling in a chicken embryo model of neoplasia

ABSTRACTHOX transcription factors are members of an evolutionarily conserved family of proteins required for the establishment of the anteroposterior body axis during bilaterian development. Although they are often deregulated in cancers, the molecular mechanisms by which they act as oncogenes or tumor suppressor genes are only partially understood. Since the MAPK/ERK signaling pathway is deregulated in most cancers, we aimed at apprehending if and how Hox proteins interact with ERK oncogenicity.Using an in vivo neoplasia model in the chicken embryo that we have developed, consisting in the overactivation of the ERK1/2 kinases in the trunk neural tube, we analyzed the consequences of HOXB8 gain of function at morphological and transcriptional level in this model. We found that HOXB8 acts as a tumor suppressor, counteracting ERK-induced neoplasia. HOXB8 tumor suppressor function in this model relies on a large reversion of the oncogenic transcriptome induced by ERK. In addition to showing that HOXB8 protein controls the transcriptional responsiveness to ERK oncogenic signaling, our study identified new downstream targets of ERK oncogenic activation in an in vivo context that could provide clues for therapeutic strategies.</jats:p

HOXB8 Counteracts MAPK/ERK Oncogenic Signaling in a Chicken Embryo Model of Neoplasia

HOX transcription factors are members of an evolutionarily conserved family of proteins required for the establishment of the anteroposterior body axis during bilaterian development. Although they are often deregulated in cancers, the molecular mechanisms by which they act as oncogenes or tumor suppressor genes are only partially understood. Since the MAPK/ERK signaling pathway is deregulated in most cancers, we aimed at apprehending if and how the Hox proteins interact with ERK oncogenicity. Using an in vivo neoplasia model in the chicken embryo consisting in the overactivation of the ERK1/2 kinases in the trunk neural tube, we analyzed the consequences of the HOXB8 gain of function at the morphological and transcriptional levels. We found that HOXB8 acts as a tumor suppressor, counteracting ERK-induced neoplasia. The HOXB8 tumor suppressor function relies on a large reversion of the oncogenic transcriptome induced by ERK. In addition to showing that the HOXB8 protein controls the transcriptional responsiveness to ERK oncogenic signaling, our study identified new downstream targets of ERK oncogenic activation in an in vivo context that could provide clues for therapeutic strategies.</jats:p

HOXB8 Counteracts MAPK/ERK Oncogenic Signaling in a Chicken Embryo Model of Neoplasia

International audienceHOX transcription factors are members of an evolutionarily conserved family of proteinsrequired for the establishment of the anteroposterior body axis during bilaterian development.Although they are often deregulated in cancers, the molecular mechanisms by which they act asoncogenes or tumor suppressor genes are only partially understood. Since the MAPK/ERK signalingpathway is deregulated in most cancers, we aimed at apprehending if and how the Hox proteinsinteract with ERK oncogenicity. Using an in vivo neoplasia model in the chicken embryo consistingin the overactivation of the ERK1/2 kinases in the trunk neural tube, we analyzed the consequencesof the HOXB8 gain of function at the morphological and transcriptional levels. We found that HOXB8acts as a tumor suppressor, counteracting ERK-induced neoplasia. The HOXB8 tumor suppressorfunction relies on a large reversion of the oncogenic transcriptome induced by ERK. In additionto showing that the HOXB8 protein controls the transcriptional responsiveness to ERK oncogenicsignaling, our study identified new downstream targets of ERK oncogenic activation in an in vivocontext that could provide clues for therapeutic strategies