Regulation of Pattern Formation by the Interaction between Growth Factors and Proteoglycans

During early development, a series of cell-to-cell interactions take place in the patterning germ layers by “morphogens”. Morphogens are emanated from one population of cells and act on the other population of cells and believed to direct cells to give rise to a variety of cell types. It is hypothesized that a gradient of morphogen activity induces target genes in responding cells with different thresholds of response to the morphogen, which eventually leads to the patterning of tissues. That is, extracellullar ligand signals are interpreted by target cells by cell surface receptors and cytoplasmic signal transducers causing transcriptional change as a read-out for cell differentiation. Polypeptide growth factors including the TGF-β superfamily of ligands have been implicated as morphogens in the patterning of tissues during early embryo-genesis. This is well explained in Xenopus embryo; activin that belongs to the TGF-β superfamily, induces goosecoid, an organizer-specific homeobox gene that marks dorsal most mesoderm at high concentrations and Xenopus brachyury (Xbra), a pan mesodermal marker gene encoding T-box protein at lower doses. Thus, it is suggested that a concentration gradient of activin patterns mesoderm. More recently, Cyclops and Squint, two Nodal-related TGF-β signals have been found to be required for mesoderm formation and patterning in zebrafish [24]. It has also been shown that only Squint can function as a direct long-range signal [8], whereas different levels of both Squint and Cyclops can induce different downstream genes.