Researchers Uncover Remarkable Developmental Pathway

Howard Hughes Medical Institute researchers have discovered an important regulatory pathway that enables frog embryos to develop normally even after being split in half -- as happens in the development of identical twins. The researchers said their findings suggest that efforts to apply embryonic stem cells therapeutically to regenerate damaged or diseased tissue may have to overcome similar self-regulatory mechanisms present in stem cells. Such mechanisms might otherwise drive stem cells to attempt to differentiate into embryos with many cell types, rather than restricting themselves to a desired single type of tissue. The researchers, graduate student Bruno Reversade and HHMI investigator Edward M. De Robertis, both at the University of California at Los Angeles, published their findings in the December 16, 2005, issue of the journal Cell. The experiments were conceived in an attempt to learn more about the mechanisms underlying the establishment of a morphogenetic field. This field consists of a gradient of regulatory proteins that aids in organizing the differentiation of embryonic cells and gives an organism its overall shape. Although researchers had known that morphogenetic fields were responsible for the embryo's remarkable resiliency, very little was understood about how they function at the molecular level, said De Robertis. For their studies, Reversade and De Robertis used early embryos of the African toad Xenopus. Widely used in embryological studies, Xenopus embryos are easy to grow and can be manipulated by tissue transplantation techniques. The researchers studied Xenopus embryos in the blastula stage, which resembles a hollow sphere of a few thousand cells. The scientists were seeking to understand more about the regulatory role of a family of proteins called bone morphogenetic proteins (BMPs). Certain BMPs are known to be key regulators of the dorsoventral (back-to-belly) patterning of embryos. In such patterning, dorsal cells differentiate into neural cells and ventral cells become epidermal cells.