Abstract
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.
Highlights
Classical embryologists postulated over 100 years ago that cells in a developing multicellular organism communicate with each other: some cells emit signals, inducers, that elicit specific changes in the receiving target cells
One of the classical paradigms for HH signalling in the vertebrate embryo is the ventral neural tube which is exposed to SHH that is released from the notochord and that induces floor plate cells, motor neurons and different types of ventral interneurons of the developing spinal cord [48]
High levels of SHH signalling from the notochord induce floor plate identity at early stages of neural development whereas comparable doses induce ventral interneurons at later stages, indicating that neural progenitors lose the competence for floor plate induction [111]
Summary
Classical embryologists postulated over 100 years ago that cells in a developing multicellular organism communicate with each other: some cells emit signals, inducers, that elicit specific changes in the receiving target cells. 2. Cellular responses may depend on cell-intrinsic factors that reflect the context of the responding signal brings us back to the idea of cellular competence: cells that respond differently to a given cell, its location and developmental history (Figure 1B). Cellular responses may depend on cell-intrinsic factors that reflect the context of the responding signal brings us back to the idea of cellular competence: cells that respond differently to a given cell, its location and developmental history (Figure 1B) This contextual ability to respond to a signalbrings display competence for thiscompetence: signal. Differential competence can be defined as a property inducer, a non cell-autonomous factor. We that discuss establishthe such differential competence review what is known about the what mechanisms by about which will factors that establish such and differential competence and review is known they could change response of a cell to HH. The mechanisms by the which they could change the response of a cell to HH
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