Modern Approaches to Vertebrate Segmentation

TOPICAL COLLECTIONS

Guest Editors

Olivier Pourquie

Harvard Medical School, Department of Genetics; Brigham and Women's Hospital, Department of Pathology

Olivier Pourquie is Professor in the Department of Genetics at Harvard Medical School and Professor of Pathology at the Brigham and Women’s Hospital. He was the director of the Institute for Genetics and Molecular and Cellular Biology (IGBMC) in France, and, before that, a Howard Hughes Medical Institute Investigator at the Stowers Institute for Medical Research in Kansas City. The Pourquie laboratory is a world leader in vertebrate musculo-skeletal axis development. Using chicken and mouse embryos as model systems, they combine developmental biology and genomic approaches to study patterning and differentiation of the precursors of muscles and vertebrae. They also develop quantitative approaches at the interface with physics to study morphogenesis of the vertebral column. While most of this work is being carried out in vivo, they also develop protocols to recapitulate these early developmental processes in vitro using mouse and human embryonic or reprogrammed stem cells. They are also turning to translational approaches, using their understanding of early development to produce cells of the muscle and vertebral lineages in vitro from pluripotent cells to study human diseases of the musculo-skeletal axis and for cell therapy approaches. Dr. Pourquie has authored more than 100 peer-reviewed publications. He is an elected member of the European Molecular Biology Organization, the Academia Europaea, and the U.S. National Academy of Sciences. His work on the segmentation clock that controls the periodicity of vertebrae was recognized as one of the milestones in developmental biology of the 20th century by Nature Magazine. Pourquie graduated as an engineer in France and trained with Nicole Le Douarin in Paris.

Margarete Diaz Cuadros

Harvard Medical School, Department of Genetics; Brigham and Women's Hospital, Department of Pathology

Margarete is a PhD student in the Biological and Biomedical Sciences (BBS) program at Harvard Medical School, where she is a member of the Developmental and Regenerative Biology community. Born and raised in Lima, Peru, she came to the US to pursue her undergraduate studies at Columbia University in New York City. She received her BA in 2014, having completed a major in Biochemistry and a minor in Evolutionary Biology of the Human Species. While at Columbia, she spent four years in Dr. Martin Chalfie's laboratory investigating neuronal subtype differentiation in the nematode Caenorhabditis elegans. Her research elucidated new mechanisms guiding neuronal outgrowth and polarity. As a graduate student in Dr. Olivier Pourquie's laboratory, she has developed in vitro systems for the recapitulation of the mammalian segmentation clock based on pluripotent stem cells. Her PhD work has resulted in the first live characterization of the human segmentation clock, an important contribution to human developmental biology. Margarete is also Director of the Research Experience for Peruvian Undergraduates (REPU) program, which seeks to increase the representation of Latin American students in scientific research. In the future, she hopes to continue an academic path with strong teaching and mentoring components.

Collection Overview

The bodies of vertebrate animals are organized into segments along the anterior-posterior body axis. During development, segments are established through the rhythmic and sequential formation of somites in the paraxial mesoderm. At the molecular level, a network of oscillating genes known as the segmentation clock is responsible for the periodicity of somitogenesis. This clock was initially discovered in chicken embryos in 1997 and has since been studied in a variety of organisms, including mouse, zebrafish, snakes, and lizards. Nevertheless, the inherent limitations of experimenting with somitogenesis-stage embryos have catapulted the advent of novel ex vivo and in vitro techniques to model and study the segmentation clock. These techniques encompass the culture of presomitic mesoderm cells outside the embryo, as well as the development of two- and three-dimensional differentiation systems based on mouse and human pluripotent stem cells. The latter include the establishment of paraxial mesoderm organoids and gastruloids that recapitulate not only oscillatory gene expression, but also morphological somite formation. Such modern approaches to vertebrate segmentation have opened new doors that will help us unravel the genetic, cellular, and mechanical processes that underlie somitogenesis. By exploiting human pluripotent stem cells, directed differentiation techniques have also enabled us to study human development directly and even model human diseases such as scoliosis. The present JoVE Methods Collection brings together these new experimental approaches in vertebrate segmentation.