A neural crest perspective on craniofacial development/ La perspective de la crête neurale sur le développement cranio-facial

Seminar organized by Philippe Soriano and Marianne Bronner, from 10 – 15 October 2022.

Participants

Igor ADAMEYKO (Karolinska Institutet, Stockholm, Sweden), Marianne BRONNER (California Institute of Technology, Pasadena, USA), Robert CERNY (Charles University in Prague, Czech Republic), D’Juan FARMER (University of California, Los Angeles, USA), Robb KRUMLAUF (Stowers Institute for Medical Research, Kansas City, USA), Carole LABONNE (Northwestern University, Evanston, USA), Hannah LONG (University of Edinburgh, United Kingdom), Roberto MAYOR (University College, London, United Kingdom), Anne-Hélène MONSORO-BURQ (Université Paris-Saclay, Institut Curie, Paris, France), Filippo RIJLI (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland), Megan ROTHSTEIN (Harvard University, Boston, USA), Licia SELLERI (University of California, San Francisco, USA), Marcos SIMOES COSTA (Harvard University, Boston, USA), Lukas SOMMER (University of Zurich, Switzerland), Philippe SORIANO (Icahn School of Medicine at Mount Sinaï, New York, USA), Paul TRAINOR (Stowers Institute for Medical Research, Kansa City, USA), Antoine ZALC (Institut Cochin, Paris, France).

Summary

Neural crest cells (green) in craniofacial structures of FGF receptors mutant mice.

The neural crest is an embryonic stem cell population that migrates throughout the embryo to form a wide range of derivatives, including much of the head skeleton. A group of seventeen investigators, ranging from senior experts in the field to starting faculty and advanced graduate students, met from October 10-15, 2022, in the unique environment provided by Les Treilles, to enable in depth discussions that led to detailed insights into the secrets of neural crest and craniofacial development. This meeting brought together a highly international group of scientists from North America and Europe with a common interest in neural crest cells. Most importantly, all attendees were asked to focus on the interplay between what is known regarding early neural crest development and how this translates into the events that lead to formation of craniofacial structures. To this end, each invitee presented an hour-long presentation including ample discussion time. The presentations provided valuable insights into how errors that occur at early developmental stages may affect proper formation of facial structures and lead to human birth defects. While neural crest and craniofacial researchers are studying similar cell types at different developmental stages, in the past there has often been little interactions between the two communities. At Les Treilles, this group participated in active exchange of ideas that highlighted their common interests, stimulated new ideas, shared the latest technologies and promoted numerous collaborations. The meeting was a great success with attendees noting that it was the best meeting they had ever attended! We are extremely grateful to the Fondation des Treilles for making this excellent meeting possible.

Résumé

La crête neurale est une population de cellules embryonnaires souches qui migrent dans tout l’embryon pour former une grande diversité de dérivés, y compris une grande partie du squelette de la tête. Un groupe de dix-sept chercheurs, experts expérimentés dans le domaine, professeurs débutants et étudiants avancés, s’est réuni du 10 au 15 octobre 2022 dans l’environnement unique fourni par La Fondation des Treilles.  Les discussions détaillées ont conduit à des connaissances approfondies sur les secrets de la crête neurale et du développement craniofacial. Cette réunion a réuni un groupe international de scientifiques d’Amérique du Nord et d’Europe ayant un intérêt commun pour les cellules de la crête neurale. De plus, tous les participants ont été invités à se concentrer sur l’interaction entre ce que l’on sait concernant le développement précoce de la crête neurale et la manière selon laquelle ces événements conduisent à la formation de structures craniofaciales. Dans ce but, chaque participant a donné une présentation d’une heure comprenant un temps de discussion suffisant. Les présentations ont fourni des informations précieuses sur la manière dont les erreurs qui se produisent aux premiers stades du développement peuvent affecter la formation correcte des structures faciales et conduire à des malformations congénitales humaines. Alors que les chercheurs sur la crête neurale et le développement craniofacial étudient des types de cellules similaires à différents stades de développement, il y a eu peu d’interactions entre les deux communautés par le passé. Aux Treilles, ce groupe a participé à un échange d’idées actif qui a mis en valeur leurs intérêts communs, stimulé des nouvelles idées, permis de partager les dernières technologies et favorisé de nombreuses collaborations. La réunion a été un grand succès, les participants notant qu’il s’agissait de la meilleure réunion à laquelle ils aient jamais assisté ! Nous sommes extrêmement reconnaissants à la Fondation des Treilles pour avoir rendu cette excellente rencontre possible.

Report

The evolutionary success of vertebrates is intimately associated with acquisition of the neural crest (NC), a stem-cell population with remarkable migratory potential and the ability to form a vast array of derivatives. The neural crest contributes to numerous cell types in vertebrate embryos including cartilage and bone of the face, peripheral ganglia, and melanocytes. The regulatory machinery controlling neural crest formation and diversification includes an intricate array of transcription factors and signaling molecules, comprising a complex gene regulatory network (GRN). These act in concert to endow the neural crest with its defining features.

During a conference held from October 10-15, 2022, at the Fondation des Treilles, 17 investigators from diverse regions of the North American and Europe came together to discuss the role of the neural crest in forming the craniofacial skeleton giving interactive talks and having extensive and excellent discussions.

The meeting initiated with presentations of early development of the neural crest and discussions of gene regulatory mechanisms controlling the formation of this stem cell population. Presentations given by Marianne Bronner, Marcos Simoes-Costa, Anne-Hélène Monsoro-Burq and Antoine Zalc focused on early formation of the neural crest from the neural plate border to the time when these cells initiate migration. Particular focus was on transcription factors that regulate early neural crest development.

As neural crest cells migrate and colonize different parts of the embryo, they transition from migratory streams to aggregates of cells within complex structures. They then contribute to cartilage condensations in the branchial arches, to neurons and glia of peripheral ganglia, and to many organs. This process is mediated by a gene regulatory program that compartmentalizes the neural crest progenitors into territories with distinct regulatory states. Functional analysis through enhancer manipulation indicates that variation in craniofacial morphology, as well as craniofacial malformations, depend upon combined enhancer activity. Understanding how such regulatory complexity unfolds from the programs of neural crest specification and migration is a major challenge confronting neural crest biologists in years to come. To elucidate these aspects of craniofacial development, the meeting had excellent presentations from Roberto Mayor, Hannah Long, Lukas Sommer, Megan Rothstein and Paul Trainor. They discussed mechanisms that control neural crest migration, define species specific traits, lead to axial level specific neural crest populations and regulate cell survival for proper facial development.

The process of neural crest diversification initiates with the activation of differentiation circuits in subpopulations of migratory cells. These circuits are centered around transcription factors expressed by the neural crest that activate lineage-specific gene batteries. Diversification into different derivatives depends upon the interplay between the regulatory state of the migratory neural crest cells and environmental cues, often conveyed by various signaling systems. Such environmental signals, particularly interactions with other tissues, are key players in determining the fate of the migratory cells. These aspects of neural crest and craniofacial development were covered by talks from Filippo Rijli, D’Juan Farmer, Licia Selleri and Philippe Soriano. These talks elucidated the complexity regulating aspects of neural crest development and facial formation, including the role of the changing epigenetic landscape, enhancer variation in cell shape, and the important role of signaling in proper craniofacial development.

The neural crest also played an incredibly important role in evolution of vertebrates by generating the “new head” which enabled vertebrates to become excellent predators, in turn resulting in enlargement of the brain. Discussion of the importance of acquisition of the neural crest for evolution of the vertebrate craniofacial skeleton was elegantly presented by Carole LaBonne, Igor Adameyko, Robb Krumlauf and Robert Cerny. They discussed evolutionary changes in gene regulation and how this facilitates neural crest evolution and multipotency.

Because neural crest cells are involved in many birth defects, including cleft lip and palate, and cancers (e.g. melanoma, neuroblastoma), the results discussed at our conference on normal craniofacial development are highly relevant to mistakes that result in birth defects as well as neural crest-derived tumors. Taken together, this conference resulted in deep insights into neural crest and craniofacial development from a modern genomic perspective that promises to produce long-lasting collaborations and exchanges of idea.

Criteria used for speaker selection

We used several criteria that explain the policy used to select speakers:

1. We wanted investigators working in the field of early neural crest, craniofacial development, and evolution. Accordingly, early development of the neural crest was represented by Anne-Hélène Monsoro-Burq, Carole LaBonne, Megan Rothstein, Marcos Simoes-Costa, and Antoine Zalc.
2. Experts in craniofacial development included Philippe Soriano, Filippo Rijli, Paul Trainor, Licia Selleri, Hannah Long, D’Juan Farmer and Robb Krumlauf.
3. In addition, we invited individuals who are working on how neural crest cells migrate to the final sites (Roberto Mayor), how they differentiate into appropriate and varied derivatives (Lukas Sommer) as well as on how their stem cell properties are acquired and how they have evolved (Igor Adameyko, Marianne Bronner, Robert Cerny).

 Retrouvez la présentation vidéo du séminaire par Philippe Soriano et Marianne Bronner sur notre chaîne Youtube.