EMBRYONIC DEVELOPMENT OF THE AXIAL SKELETON AND MUSCLE

The vertebral column and axial skeletal muscles develop from paired structures in the embryo, called somites. They arise from loosely packed cells which come from the primitive streak at very early stages of development. Despite considerable interest for more than a century in understanding how the segmented organization of the somites, vertebrae and axial muscles is established, the processes that control this organization are still unknown at any level: tissue, cellular or molecular. The broad aim of this research is to elucidate these control processes at all levels. This project investigates the cellular aspects, to address four fundamental questions: (a) do early somite progenitors behave as stem cells? (b) which cell population is responsible for setting up the segmental pattern? (c) is segmentation cell autonomous and/or does it involve cell sorting? and (d) does each vertebra arise from the caudal half of one somite and the rostral half of the adjacent somite, as is widely believed? To answer them, a combination of recently developed techniques will be used. They include labeling of small groups of cells with carbocyanine dyes, single cell lineage analysis by intracellular injection of a tracer, following marked cells with time-lapse video microscopy and microsurgical operations to challenge the fates of small groups of embryonic cells. Without the information that the research will yield, it will be difficult to provide direction to a search for the molecules that control these important processes. The knowledge gained will help understand developmental mutations affecting the vertebral column as well as the etiology of some frequent and severe congenital abnormalities, including scoliosis, kyphosis, lordosis, Klippel-Feil syndrome and many others.