Abstract:
:Sonic hedgehog (Shh) signaling from the posterior zone of polarizing activity (ZPA) is the primary determinant of anterior-posterior polarity in the vertebrate limb field. An active signal is produced by an autoprocessing reaction that covalently links cholesterol to the N-terminal signaling moiety (N-Shh(p)), tethering N-Shh(p) to the cell membrane. We have addressed the role played by this lipophilic modification in Shh-mediated patterning of mouse digits. Both the distribution and activity of N-Shh(p) indicate that N-Shh(p) acts directly over a few hundred microns. In contrast, N-Shh, a form that lacks cholesterol, retains similar biological activity to N-Shh(p), but signaling is posteriorly restricted. Thus, cholesterol modification is essential for the normal range of signaling. It also appears to be necessary for appropriate modulation of signaling by the Shh receptor, Ptc1.
journal_name
Celljournal_title
Cellauthors
Lewis PM,Dunn MP,McMahon JA,Logan M,Martin JF,St-Jacques B,McMahon APdoi
10.1016/s0092-8674(01)00369-5subject
Has Abstractpub_date
2001-06-01 00:00:00pages
599-612issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(01)00369-5journal_volume
105pub_type
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