Differential Cellular Responses to Hedgehog Signalling in Vertebrates—What is the Role of Competence?

• Main Authors: Clemens Kiecker, Anthony Graham, Malcolm Logan
• Format: Article
• Language: English
• Published: MDPI AG 2016-12-01
• Series: Journal of Developmental Biology
• Subjects: chick embryo; Drosophila; iroquois; IRX; limb bud; morphogen; mouse; neural tube; proliferation; temporal adaptation; zebrafish
• Online Access: http://www.mdpi.com/2221-3759/4/4/36

A surprisingly small number of signalling pathways generate a plethora of cellular responses ranging from the acquisition of multiple cell fates to proliferation, differentiation, morphogenesis and cell death. These diverse responses may be due to the dose-dependent activities of signalling factors, or to intrinsic differences in the response of cells to a given signal—a phenomenon called differential cellular competence. In this review, we focus on temporal and spatial differences in competence for Hedgehog (HH) signalling, a signalling pathway that is reiteratively employed in embryos and adult organisms. We discuss the upstream signals and mechanisms that may establish differential competence for HHs in a range of different tissues. We argue that the changing competence for HH signalling provides a four-dimensional framework for the interpretation of the signal that is essential for the emergence of functional anatomy. A number of diseases—including several types of cancer—are caused by malfunctions of the HH pathway. A better understanding of what provides differential competence for this signal may reveal HH-related disease mechanisms and equip us with more specific tools to manipulate HH signalling in the clinic.