Although all of these organisms develop from essentially the same set of building blocks, it has long been a mystery how cell and organism size is regulated.

Recent research has pointed to an important role for signaling pathways in size regulation, particularly insulin signaling. Now, a study published in the May issue of Developmental Cell describes a remarkable observation that has led to discovery of an additional signaling pathway that regulates cell and animal size during development.

The study, led by Dr. Jeffrey Settleman of Harvard Medical School, was designed to examine the function of a protein called p190-B Rho-GAP. This molecule is a known activator of the important family of Rho proteins that have been implicated in many cellular processes including motility, gene expression, proliferation and cellular shape change.

The scientists generated mice that were lacking p190-B Rho-GAP and made the startling discovery that they were 30% smaller than their normal counterparts.

Interestingly, almost every organ examined exhibited a reduction in size, suggesting an organism-wide mechanism for regulation of body growth. The physical characteristics of the mice were very similar to those previously described for mice deficient in a common signaling protein called CREB (cAMP response element binding protein).

The p190-B Rho-GAP-deficient mice exhibited a reduction of activated CREB and the researchers demonstrated that the cell size defect could be rescued by adding activated CREB. Further, when activated Rho or defective CREB was added to normal cells growing in the lab, they manifested a reduction in size.

These results indicate that Rho and CREB are novel regulators of cell and animal size in the developing mouse.

This is the first time that Rho has been implicated in control of cell size. The authors conclude that Rho modulates a chemical growth signal from the cell membrane to CREB.

Although the researchers are careful to caution that the signaling pathway is extremely complex, they propose that their results are a significant step forward in the understanding of what molecules contribute to regulation of size.

Future studies will make use of these new findings to further define the molecular mechanisms that regulate the size of cells, organs and organisms during development.


[Contact: Dr. Jeffrey Settleman]

10-May-2002