om stem cells to fully-developed types in the blood. Several types of blood cells vanished entirely; the same thing happened to more basic cell types higher up in the blood lineage hierarchy. Particular kinds of stem cells disappeared from the bone marrow of the mice. Others were too frequent. Bone marrow cells didn't develop into myeloid and red blood cells. B- and T-cells were also blocked at early stages, but in a different way. This hints that they may be controlled by other protein links in the Wingless pathway as well. Perhaps most strikingly, beta-catenin appears to make cells take decisions about their fate before they leave the stem cell compartment in the bone marrow, something so far not thought to occur.

The study proves that beta-catenin plays a central role in determining whether blood cells form or not. On the other hand, an overactive Wingless pathway doesn't seem to damage cells that already exist. Thus beta-catenin seems to be a decision-maker, a selector of how information gets routed within the cell, rather than something which maintains the vitality of existing cells.

Nerlov compares the breakdown to people standing at a fork in a labyrinth, hesitating before they go on. "We know there are strong connections to cells' decisions to divide, to develop or to die. If cells don't commit themselves to the right developmental path at the right time, they're very likely to die or to begin an inappropriate type of reproduction. Acute leukemias and other forms of cancer cells derive from defects such as this. Understanding the processes by which they form will require pinpointing the forks in the road where things go wrong."

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Contact: Anna-Lynn Wegener
wegener@embl.de
296-221-387-452
European Molecular Biology Laboratory
3-Sep-2006

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