Discovering how cell signaling encodes positional information for segmental determination and pattern scaling
Signaling is fundamental for cells to sense their micro-environment and communicate with each other during development, tissue repair, immunity as well as normal tissue homeostasis. How information is encoded to instruct signal-receiving cells is a critical question in biology and bio-engineering. Here we studied this important problem in the context of patterning the vertebral column during embryonic development.
Pattern formation is universal; organisms display characteristic patterns throughout the metazoan. From the earliest days of embryology, it has been clear that the remarkable robustness of pattern formation is primarily manifest at the level of relative, not absolute, pattern, which is also called pattern scaling. Identifying the mechanisms governing pattern formation and scaling during development is a longstanding interest in biology.
Somitogenesis is an important example of repetitive pattern formation. Somitogenesis is very versatile. Different segment numbers and periodicity among species exist but they are also very precise. The same segment number and size distribution exist within each species, per the 2008 publication (Gomez et al, Nature). Embryos form a fixed number of patterns, or segments, and the sizes of patterns scale with body or tissue sizes even when total cell numbers, cell sizes or growth rates are changed experimentally (Cooke J, 1975 and Cooke J, 1981, Nature).
Wolpert’s positional information model (1969) proposes that commitment of a cell to a given state depends on its interpretation of a constant threshold of a graded morphogen across tissue.
Clock and wavefront (CW) model was built on the positional information model to explain periodic segmentation of somites by the interaction of the segmentation clock and a traveling morphogen gradient (wavefront) (Cooke & Zeeman, 1976).
Despite decades-long efforts, how positional information for segmentation is encoded by cell signaling remained elusive. We aspire to discover the underlying mechanism of this fundamental question.
