ROCK and Rho in 3D

In This Issue In This Issue BMP in a hairy situation morphogen must be both off and on for hairs to grow, according to Kobielak et al. on page 609. Their studies of bald mice reveal that bone morphogenetic protein (BMP) controls the switch from dividing to differentiating hair cells by working at the right time and place. Hair cells arise from a pool of epithelial precursors that first proliferate and then differentiate to form the hair channel and the hair itself. Proliferation signals originate from a set of mesen-chymal cells called the dermal papillae (DP) at the base of the hair follicle. Further up the follicle, differentiation is a response to Wnt signaling that works through stabilized ␤-catenin and Lef1 to turn on genes such as hair keratins. Now, Kobielak et al. find that the later differentiation depends on both the absence of BMP signaling during proliferation, which allows a buildup of Lef-1, and the presence of BMP signaling later on, A ROCK and Rho in 3D reast cells pull on their surroundings to sense whether to proliferate or differentiate, according to Wozniak et al. on page 583. This matrix-sensing pathway may explain why carcinoma risk is increased in women with fibrous breast tissue. Differentiation of breast epithelial cells into tubules occurs in vitro if the cells are cultured in a 3D collagen matrix floating in medium. If the same matrix is made more rigid by attachment to a surface, tubulogenesis is disrupted, indicating that breast cells sense the flexibility of their surroundings. Wozniak et B In a rigid matrix (right), cells strengthen adhesions (arrows) with FAK (red) and do not form tubules. al. now find that the small GTPase Rho and its effector, ROCK, are essential for the cells to pull against the matrix and to respond to the resistance encountered. The breast epithelial cells attach to their collagenous matrix via integrin receptors, which regulate Rho/ROCK-mediated actin–myosin contractility. The authors show that if the cells are able to contract their matrix, as in the floating 3D gels, Rho is down-regulated and the focal adhesion protein FAK is scattered throughout the cell. As expected, these cells differentiate into tubules—a process that may require matrix flexibility to work efficiently. In contrast, if the matrix is made too rigid for cells to contract (e.g., by increasing collagen levels in the floating gels), Rho activity remains high and FAK is found at …