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Rockefeller scientists identify 'natural' proteins that push stem cells to produce hair, not skin

change shape, so that they can zip up tight, locking together through all the many E-cadherin proteins found on the outside of the cell, he says.

Any extra beta-catenin produced within these cells that is not used to link E-cadherin to the actin cytoskeleton is quickly gobbled up by special enzyme "machinery" within the cell body, the researchers say. These stem cells become skin.

Fuchs and her team then clarified what happens when that same cell receives growth signals to change shape and become a hair follicle. After years of research using a series of knockout mice and lab experimentation with their stem cell cultures, the researchers found that both the Wnt and noggin growth factors are needed as simultaneous input to the stem cell.

First, noggin signals the cells to make the Lef-1 transcription factor. Then, the Wnt protein prompts a cascade of signals that turn off the machinery that degrades excess beta-catenin. This allows beta-catenin proteins to build up inside the stem cell. This excess beta-catenin binds to Lef-1.

Once in the nucleus of the stem cell, the beta-catenin/Lef-1 complex reduces the transcription of the gene that produces E-cadherin. By reducing the ongoing synthesis of the E-cadherin protein that is constantly needed to keep cells stuck together, the cell can loosen from others around it. Without as much E-cadherin there to bind to the beta-catenin-actin cytoskeleton complex, the structure of the cell changes, allowing it to migrate down between the other stem cells, Fuchs says.

Using mice genetically altered not to produce noggin, the researchers showed that the Lef-1 transcription factor was not being produced. Experiments in which the level of E-cadherin was kept high blocked production of hair follicles, because E-cadherin production must be reduced in order for stem cells to loosen and reorganize to form follicles. Together these experiments verified the importance of the beta-catenin/Lef-1 pathwa
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Contact: Joseph Bonner
bonnerj@mail.rockefeller.edu
212-327-8998
Rockefeller University
19-Mar-2003


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