April 10, 2017

Meet Maryline Minoux

Maryline Minoux is a dentist and visiting scientist in Filippo Rijli’s group studying the molecular mechanisms involved in craniofacial morphogenesis. Recently, she published the results of an elaborate study that identified an epigenetic mechanism in neural crest cells regulating the formation of facial features

Q: You work as Professor at the Faculty of Dental Medicine of Strasbourg and pursue basic research projects in the group of Filippo Rijli at the FMI. What is your motivation to examine basic developmental questions?
Maryline Minoux: My main motivation is my curiosity, but it is also quite exciting to be the first to understand a mechanism that controls head development.
As a dentist, I came naturally to this topic. Indeed, from a developmental point of view, the odontoblasts that are involved in the formation of the teeth and the osteoblasts and chondroblasts that form the skeletal and cartilaginous structures of the face derive from the same cell type: the cranial neural crest cells. The development of these structures is linked and many syndromes with dental abnormalities include ear or bone defects resulting in face malformations. My interest is then to better understand craniofacial abnormalities of genetic origin.
Studying the neural crest cells is also of particular interest for stem cell therapies. Indeed, the neural crest cells are multipotent cells displaying features close to the embryonic stem cells. Understanding the molecular mechanisms that control the developmental program of the neural crest cells is then an essential prerequisite for the development of therapeutic approaches allowing dental tissue regeneration.

Q: Recently you have found an epigenetic mechanism that controls the formation of our facial features. What was the biggest challenge in this project? And what helped you take it up?
In the last 30 years or so, embryologists have been puzzled by the question of how neural crest cells ‘know’ how to make the right craniofacial structure in the right place, to assemble a harmonious face. We decided to take the hard road to tackle this problem, and isolated neural crest subpopulations from prenatal embryos during the formation of the face to analyze their epigenome.
It all started with our discovery that the genes involved in positional identity of the early post-migratory neural crest cells had poised promoters in the cell subpopulation(s) in which they were silenced. We therefore hypothesized that this chromatin organization underlies the positional plasticity of the neural crest cells and was already present in the pre-migratory neural crest cell progenitors. The first challenge was then to collect enough progenitors from mouse embryos at 8.5 days of development, to perform ChIP-seq. The second challenge was to set up sequential H3K27me3-H3K4me2 ChIP-seq, to prove genome wide that H3K27me3 and H3K4me2 histone marks co-localized at the same location and in the same cells. To overcome technical hurdles, I could always count on the support and advice from my colleagues from the lab and the FMI facilities. In addition, the computational analysis of our huge genome wide data sets was a challenge that we could not have tackled without the expertise of Michael Stadler. It was a great opportunity for me to collaborate with him. And of course, without Filippo’s constant support and enthusiasm nothing would have been possible.

Q: How do the insights from basic research influence your work with patients?
There is a good complementarity between my clinical and my research activities. Indeed, at the Faculty of Dental Medicine of Strasbourg, I am taking care of patients from the “Reference Center for Rare Dental Genetic Diseases”. These patients display several dental abnormalities, including agenesis and/or shape defects. For the moment, insights from basic research in the field of developmental biology do not yet allow repairing or replacing the affected teeth ad integrum. My research activities however improve how I am taking care of these patients. First, the relationship with them is facilitated. Then, I can discuss with these patients the possibilities of genetic testing, which can direct them to more appropriate prevention and treatment options. To this, a good understanding of the molecular mechanisms involved in craniofacial development is mandatory. Basic research is then fully relevant for patient-care.

Q: Basic research, work as a dentist and running a family, how do you juggle these three responsibilities? And what would you recommend to young scientists who are at the start of their career and maybe want to have a family?
This question is particularly important, especially for women who desire to have a family. For female scientists, I do not think that there is a “best time” to have children. Each personal path is different. However, I believe that the desire to succeed professionally can be compatible with having a family.
Raising children in a competitive professional environment however requires strong motivation and great organizational skills, the full involvement of both parents in daily home-tasks, and a certain degree of flexibility to organize working hours.

Q: Who has inspired you during your career and why?
The scientist who has inspired me at the very beginning of my career was Pierre Chambon. He was at the same time Professor at the Faculty of Medicine in Strasbourg and founder of the IGBMC in Strasbourg, the largest French research unit in molecular biology. The way he thinks about science and his ability to identify what would be important next in a scientific field, is always impressive.
I also strongly admire Nicole Le Douarin, who contributed seminally to the field of neural crest cells. Her work on craniofacial development was key in providing the basic framework on which to build our work hypothesis. I had the chance to meet and talk with her recently at the French National Academy of Science: This was a day to remember.

» More about Maryline’s work
» The Rijli lab

Publication
Minoux M, Holwerda S, Vitobello A, Kitazawa T, Kohler H, Stadler MB, Rijli FM, (2017) Gene bivalency at polycomb domains regulates cranial neural crest positional identity. Science 355:eaal2913