[HTML][HTML] Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning

S Ahn, AL Joyner - Cell, 2004 - cell.com
S Ahn, AL Joyner
Cell, 2004cell.com
In the vertebrate limb, the posteriorly located zone of polarizing activity (ZPA) regulates digit
identity through the morphogen Sonic Hedgehog (Shh). By genetically marking Shh-
responding cells in mice, we have addressed whether the cumulative influence of positive
Shh signaling over time and space reflects a linear gradient of Shh responsiveness and
whether Shh could play additional roles in limb patterning. Our results show that all posterior
limb mesenchyme cells, as well as the ectoderm, respond to Shh from the ZPA and become …
Abstract
In the vertebrate limb, the posteriorly located zone of polarizing activity (ZPA) regulates digit identity through the morphogen Sonic Hedgehog (Shh). By genetically marking Shh-responding cells in mice, we have addressed whether the cumulative influence of positive Shh signaling over time and space reflects a linear gradient of Shh responsiveness and whether Shh could play additional roles in limb patterning. Our results show that all posterior limb mesenchyme cells, as well as the ectoderm, respond to Shh from the ZPA and become the bone, muscle, and skin of the posterior limb. Further, the readout of Shh activator function integrated over time and space does not display a stable and linear gradient along the A-P axis, as in a classical morphogen view. Finally, by fate mapping Shh-responding cells in Gli2 and Gli3 mutant limbs, we demonstrate that a specific level of positive Hh signaling is not required to specify digit identities.
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