During the third week of development, the cells of the human embryo get organized into three layers – ectoderm, mesoderm, and endoderm. These three layers form the foundation of the tissues that ultimately make up the body. The mesoderm forms all the connective tissues of the body, like the adipose tissue, bones, and cartilages. It differentiates into three columns, the paraxial, intermediate, and lateral plate mesoderms. Afterward, the paraxial mesoderm assumes a segmented appearance creating the somites. These somites ultimately develop, forming rigid structures arranged to form a flexible column that supports the skeleton of the human being, protects the spinal cord and the nerves which arise from it, and acts as a platform on which the muscles act to move. This rigid but fairly flexible column, popularly known as the backbone or spine is called the spinal column. The significance of this column can’t be overemphasized as a deformity in its development may result in conditions that affect posture, predispose the spinal cord and nerves to damage, or affect movement.
To further understand the development of the spinal column, researchers at Ebisuya Group at EMBL Barcelona have developed a 3D in vitro model that mimics how the somites that give rise to the spinal column develop during human embryonic development. This study would not only promote our understanding of the spine but also provide answers to questions that baffle us about its defects.
Mimicking somitogenesis, a guide to understanding the spine
Somitogenesis encompasses the process of somite formation, patterning, differentiation, and maturation to form somite-derived tissues (viz, the spinal column, ribs, and skeletal muscles). To mimic this process, researchers cultured human-induced pluripotent stem cells (hiPSC) in the presence of a myriad of appropriate signaling molecules that induce cell differentiation. Three days later, they discovered that the cells began to lengthen, creating anterior and posterior axes. The scientists then added a protein mixture known as matrigel. This mixture has been tagged by numerous scientists as ‘the magic powder of development’ because of its crucial role in numerous processes of development. These steps then led to the formation of somitoids (in vitro equivalents of human somite precursor structures).
The researchers went further to monitor the expression patterns of HES7, an important gene that regulates the process. They discovered clear-cut indications of ‘oscillations’, especially at the onset of somitogenesis, a clear proof that the segmentation clock also regulates somitogenesis in these somitoids. The expression of appropriate markers necessary for mutation of the cells was also observed.
What distinguishes somitogenesis in humans from other animals?
The Ebisuya group also studies how and why humans are different from other species as regards embryonic development. In 2020, they discovered that the difference lies in the period of the segmentation clock that drives somitogenesis in animals.
Several conditions arise from a defect in somitogenesis. This discovery hopes to provide answers to understanding the pathogenesis of these conditions, and providing solutions to their management and treatment.
Where does the spine come from and how can we use that knowledge to provide solutions to the anomalies of the spinal column? Part of this question has been answered by the recent discovery by the Ebisuya group. Further research promises to bring greater clarity.