Untangling signaling crosstalk during animal development

Giovanna Collu

Throughout development, only a handful of signaling pathways are used time and again to specify the full array of cell fates, ranging from thousands to billions, depending on the organism. How such diversity can be generated from a limited number of inputs is a topic of active inquiry. Emerging themes include sequential activation of pathways, for example, one pathway activating ligand expression of a second pathway, and combinatorial signaling through cooperative binding of transcription factors. Inhibitory crosstalk also exists whereby a cell can resolve two opposing inputs into a robust binary fate choice, for example, a progenitor cell’s decision to proliferate or differentiate. Notch and Wnt are two such pathways that are required for the development and maintenance of almost all human tissues. Consequently, dysregulation of either pathway leads to a wide range of diseases from congenital disorders to cancer. Notch and Wnt signaling exhibit each of the above types of interactions in a manner conserved throughout evolution. I will first provide examples of these interactions during embryonic development and adult tissue homeostasis, and then describe how we are investigating mechanisms of inhibitory crosstalk at the molecular level.

In summary, the study of signaling crosstalk during animal development is an active area of research, focusing on how a limited number of pathways can generate diverse cellular fates. Notch and Wnt signaling pathways, which are crucial for human tissue development, exhibit various types of interactions that play a role in both embryonic development and adult tissue homeostasis.