Patterning, morphogenesis and differentiation of embryos

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After fertilization an egg cleaves to form a multi-cellular embryo. The embryo becomes organized via morphogenetic processes and cellular differentiation into a complex body consisting of organs having specialized tissues. The cells of the embryo acquire specialized fates appropriate for their position in the embryo and then differentiate. This specification of fates is the result of patterning events that depend on the organization of the egg imposed during oogenesis and on cellular interactions that involve intercellular signalling molecules and their receptors. The activities of many of these signalling molecules depend on their interactions with complex sulfated proteoglycans on the surface of cells and in the extra-cellular matrix. We will investigate these events in a simple marine embryo (the sea urchin), which in many ways develops like mammalian embryos. It develops externally in sea water and is transparent, allowing microscopy examination and experimental interventions. We have found that experimental inhibition of the formation of sulfated proteoglycans disrupts the patterning of these embryos as well as some morphogenetic events, gastrulation and mouth formation in particular. We are taking advantage of information derived from the recently sequenced genome of the sea urchin to gain a better understanding of the role of sulphated proteoglycans by knocking down the expression of genes involved in their formation and modification. We hypothesize that auto-regulatory signalling by Nodal is required for establishment and maintenance of the oral-aboral (ventral-dorsal) axis and completion of gastrulation and that Nodal depends on interactions with sulfated proteoglycans to which it probably binds. We will also investigate the expression and possible roles in sea urchin embryos and larvae of genes involved in vision and hearing in higher vertebrates. These genes, including some required for retina formation in mammals and the genes of the Usher syndrome in humans, were surprisingly found in the sea urchin genome and many are expressed in embryos (which lack eyes and ears).