caa a22 4500 475845455 CHVBK 20180406123912.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1007/PL00000653 doi (NATIONALLICENCE)springer-10.1007/PL00000653 The role of cholesterol in Shh signaling and teratogen-induced holoprosencephaly [Elektronische Daten] [J. P. Incardona, H. Roelink*] Abstract.: Holoprosencephaly, or an undivided forebrain, is a complex brain malformation associated with Sonic hedgehog (Shh) mutations. Other causes of holoprosencephaly have converged upon the Shh signaling pathway: genetic and pharmacologic impairment of cholesterol synthesis, and the action of the steroidal alkaloid cyclopamine. This review focuses on recent studies aimed at determining how Shh signaling is affected by these causes of holoprosencephaly, whether they involve a common mechanism and the role played by cholesterol. Cholesterol is potentially important for both biogenesis of Shh and in signal transduction in Shh-responsive cells. Teratogens that induce holoprosencephaly appear to affect Shh signal transduction rather than Shh biogenesis. Analysis of these agents and other compounds that affect various aspects of cellular cholesterol distribution indicates that the role of cholesterol in Shh signal transduction is novel and complicated. The similarity of the Shh receptor, Patched (Ptc), to the Niemann-Pick C1 protein, which is involved in the vesicular trafficking of cholesterol, provides insight into the role of cholesterol and the action of compounds like cyclopamine. Birkhäuser Verlag Basel,, 2000 Key words. Sonic hedgehog nationallicence patched nationallicence Niemann-Pick C1 nationallicence cholesterol nationallicence cyclopamine nationallicence signal transduction nationallicence Incardona J. P. Department of Biological Structure and Center for Developmental Biology, University of Washington, Box 357420, HSB G527, Seattle (Washington 98195, USA), Fax +1 206 543 1524, e-mail: roelink@u.washington.edu, US aut Roelink* H. Department of Biological Structure and Center for Developmental Biology, University of Washington, Box 357420, HSB G527, Seattle (Washington 98195, USA), Fax +1 206 543 1524, e-mail: roelink@u.washington.edu, US aut https://doi.org/10.1007/PL00000653 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000653 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Incardona J. P. Department of Biological Structure and Center for Developmental Biology, University of Washington, Box 357420, HSB G527, Seattle (Washington 98195, USA), Fax +1 206 543 1524, e-mail: roelink@u.washington.edu, US aut NATIONALLICENCE 700 1- Roelink* H. Department of Biological Structure and Center for Developmental Biology, University of Washington, Box 357420, HSB G527, Seattle (Washington 98195, USA), Fax +1 206 543 1524, e-mail: roelink@u.washington.edu, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer