A conserved mechanism of Hedgehog gradient formation by lipid modifications

Members of the Hedgehog (Hh) family of proteins are conserved morphogens that modulate cell fates in target tissues in different developmental systems. Dysregulation of Hh signaling results in a wide range of human diseases. The mature Hh is modified by lipids in two places, with palmitate at the N-...

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Detalles Bibliográficos
Autores: Guerrero Vega, Isabel, Chiang, Chin
Tipo de recurso: artículo
Fecha de publicación:2006
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/4802
Acceso en línea:http://hdl.handle.net/10261/4802
Access Level:acceso abierto
Palabra clave:Drosophila
Hedgehog
Descripción
Sumario:Members of the Hedgehog (Hh) family of proteins are conserved morphogens that modulate cell fates in target tissues in different developmental systems. Dysregulation of Hh signaling results in a wide range of human diseases. The mature Hh is modified by lipids in two places, with palmitate at the N-terminus and cholesterol at the C-terminus. The lipid modifications are essential to the proper secretion and spreading of the morphogen throughout the extracellular matrix, interacting with heparan sulfate proteoglycans. However, the role of lipid modifications in regulating the range and activity of Hh proteins remains controversial. Here, we aim to resolve this issue by providing a model that is consistent with current and past reports. We propose that the cholesterol moiety functions to restrict the dilution and deregulated spread of the morphogen in the extracellular space