Molecular Signaling, Epithelium-to-Mesenchyme transition, and Cell Motility in Embryogenesis

Monsoro

Anne-Hélène Monsoro-Burq Team Leader

Figure 1 : Genetic network acting upstream of neural crest induction (modified from Monsoro-Burq et al., 2005 and Nichane et al. 2008).
Figure 1 : Genetic network acting upstream of neural crest induction (modified from Monsoro-Burq et al., 2005 and Nichane et al. 2008).

During embryogenesis, the epithelial-to-mesenchymal transition (EMT) is an essential morphogenetic process allowing epithelial cells to become separate migratory cells. This process is also activated when epithelial tumours develop metastases. In both cases, common gene activities such as Snail1 or Snail2 gene activation are involved. While the molecular mechanisms of Snail-induced EMT begin to be elucidated at the cellular level, little is known about the upstream regulation of these genes. To address this major challenge in developmental as well as cancer biology, the overall aim of our research is to understand how a combination of diffusible signalling molecules, multiple signal transduction pathways and their transcriptional responses are integrated and regulate Snail1/2 and other EMT-regulating factors, in normal and pathological contexts.

 

 

Monsoro2
Figure 2: Amphibian embryos (Xenopus laevis) develop externally and are very amenable to experimental manipulations. A, C: normal expression of Twist gene marks the migrating neural crest (A), which develops into derivatives such as craniofacial cartilage (C) (controls). B, D: These processes are altered if network gene activities (figure 1) are blocked. Red arrows indicate injected side.

The neural crest is a key embryonic cell population undergoing EMT. Despite a wide interest for the early steps of development of these cells and the identification of many secreted factors and genes involved in neural crest induction, our knowledge of how these signals are integrated and how these genes are organised into an epistatic cascade is poorly documented. Our aim is to provide a comprehensive understanding of the genetic network controlling early neural crest formation during development, from its induction to EMT. We focus on the genes (transcription factors mainly) and growth factors that control Snail1 and Snail2 induction, or the genes that cooperate with Snail 1/2 to complete the EMT process. By taking advantage of the multiple ways of manipulating embryogenesis in amphibian and avian embryos, we have provided the first epistatic and functional cascade of regulations upstream of Snail1/2 in neural crest induction. Our findings in amphibian embryos have provided a novel and useful framework, now confirmed in other vertebrate species. These findings will provide critical novel clues to understand neural crest formation and control of EMT on a fundamental point of view and will also identify new molecular candidates for a precocious diagnosis of tumour progression and potential therapeutic targets.

Key publications

Year of publication 2017

Jean-Louis Plouhinec, Sofía Medina-Ruiz, Caroline Borday, Elsa Bernard, Jean-Philippe Vert, Michael B Eisen, Richard M Harland, Anne H Monsoro-Burq (2017 Oct 20)

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates.

PLoS biology : e2004045 : DOI : 10.1371/journal.pbio.2004045
Ana Leonor Figueiredo, Frédérique Maczkowiak, Caroline Borday, Patrick Pla, Meghane Sittewelle, Caterina Pegoraro, Anne H Monsoro-Burq (2017 Oct 18)

PFKFB4 control of AKT signaling is essential for premigratory and migratory neural crest formation.

Development (Cambridge, England) : 4183-4194 : DOI : 10.1242/dev.157644

Year of publication 2015

Caterina Pegoraro, Ana Leonor Figueiredo, Frédérique Maczkowiak, Celio Pouponnot, Alain Eychène, Anne H Monsoro-Burq (2015 Jan 20)

PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis.

Nature communications : 5953 : DOI : 10.1038/ncomms6953

Year of publication 2013

Jean-Louis Plouhinec, Daniel D Roche, Caterina Pegoraro, Ana Leonor Figueiredo, Frédérique Maczkowiak, Lisa J Brunet, Cécile Milet, Jean-Philippe Vert, Nicolas Pollet, Richard M Harland, Anne H Monsoro-Burq (2013 May 30)

Pax3 and Zic1 trigger the early neural crest gene regulatory network by the direct activation of multiple key neural crest specifiers.

Developmental biology : 461-72 : DOI : 10.1016/j.ydbio.2013.12.010
Cécile Milet, Frédérique Maczkowiak, Daniel D Roche, Anne Hélène Monsoro-Burq (2013 Mar 18)

Pax3 and Zic1 drive induction and differentiation of multipotent, migratory, and functional neural crest in Xenopus embryos.

Proceedings of the National Academy of Sciences of the United States of America : 5528-33 : DOI : 10.1073/pnas.1219124110

Year of publication 2010

Noémie de Crozé, Frédérique Maczkowiak, Anne H Monsoro-Burq (2010 Dec 15)

Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network.

Proceedings of the National Academy of Sciences of the United States of America : 155-60 : DOI : 10.1073/pnas.1010740107
All publications