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Publication : A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers.

First Author  Zhulyn O Year  2014
Journal  Dev Cell Volume  29
Issue  2 Pages  241-9
PubMed ID  24726283 Mgi Jnum  J:213417
Mgi Id  MGI:5584329 Doi  10.1016/j.devcel.2014.03.002
Citation  Zhulyn O, et al. (2014) A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers. Dev Cell 29(2):241-9
abstractText  The patterning and growth of the embryonic vertebrate limb is dependent on Sonic hedgehog (Shh), a morphogen that regulates the activity of Gli transcription factors. However, Shh expression is not observed during the first 12 hr of limb development. During this phase, the limb bud is prepatterned into anterior and posterior regions through the antagonistic actions of transcription factors Gli3 and Hand2. We demonstrate that precocious activation of Shh signaling during this early phase interferes with the Gli3-dependent specification of anterior progenitors, disturbing establishment of signaling centers and normal outgrowth of the limb. Our findings illustrate that limb development requires a sweet spot in the level and timing of pathway activation that allows for the Shh-dependent expansion of posterior progenitors without interfering with early prepatterning functions of Gli3/Gli3R or specification of anterior progenitors.
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