Lin, A. Y. T. | bioRxiv Science

bioRxiv2020

GLI3 Processing by the Primary Cilium Regulates Muscle Stem Cell Entry into GAlert

Satellite cells are required for the growth, maintenance, and regeneration of skeletal muscle. Quiescent satellite cells possess a primary cilium, a structure that regulates the processing of the GLI family of transcription factors. Here we find that GLI3, specifically, plays a critical role in satellite cell activation. Primary cilia-mediated processing of GLI3 is required to maintain satellite cells in a G0 dormant state. Strikingly, satellite cells lacking GLI3 enter GAlert in the absence of injury. Furthermore, GLI3 depletion or inhibition of its processing stimulates symmetrical division in satellite cells and expansion of the stem cell pool. As a result, satellite cells lacking GLI3 display rapid cell-cycle entry, increased proliferation and augmented self-renewal, and markedly enhanced long-term regenerative capacity. Therefore, our results reveal an essential role for primary cilia processing of GLI3 in regulating muscle stem cell activation and fate.

cell biology↗

bioRxiv2016

Yorkie is required to restrict the injury responses in planarians

Regeneration requires the precise integration of cues that initiate proliferation, direct differentiation, and ultimately re-pattern tissues to the proper size and scale. Yet how these processes are integrated with wounding cues remains relatively unknown. The freshwater planarian, Schmidtea mediterranea, is an ideal model to study the stereotyped proliferative and transcriptional responses to injury due to its high capacity for regeneration. Here, we characterize the effector of the Hippo signalling cascade, yorkie, during planarian regeneration and its role in restricting early injury responses. In yki(RNAi) regenerating animals, wound responses are hyper-activated; the bimodal proliferation kinetics are heighted and prolonged, while the transcriptional injury responses are similarly augmented with dysregulated temporal patterns. We also uncovered novel wound-induced genes by RNAseq that are primarily associated with tissue patterning. Indeed, a high proportion of non-wound- and wound-induced patterning molecules are mis-expressed in yki(RNAi), which we demonstrate is in part due to an expanded muscle cell population. These altered injury responses have consequential effects on regenerative outcomes, specifically sensing the size of a given injury and appropriately scaling organ and tissue sizes. Taken together, our results suggest that yki functions as a key node to integrate the injury responses of proliferation, apoptosis, injury-induced transcription, and patterning to coordinate regeneration.

molecular biology↗