Integrins are required for tissue organization and restriction of neurogenesis in regenerating planarians

Abstract

Tissue regeneration depends on proliferative cells and on cues that regulate cell division, differentiation, patterning and the restriction of these processes once regeneration is complete. In planarians, flatworms with high regenerative potential, muscle cells express some of these instructive cues. Here, we show that members of the integrin family of adhesion molecules are required for the integrity of regenerating tissues, including the musculature. Remarkably, in regenerating β1-integrin RNAi planarians, we detected increased numbers of mitotic cells and progenitor cell types, as well as a reduced ability of stem cells and lineage-restricted progenitor cells to accumulate at wound sites. These animals also formed ectopic spheroid structures of neural identity in regenerating heads. Interestingly, those polarized assemblies comprised a variety of neural cells and underwent continuous growth. Our study indicates that integrin-mediated cell adhesion is required for the regenerative formation of organized tissues and for restricting neurogenesis during planarian regeneration.

An X-ray shielded irradiation assay reveals EMT transcription factors control pluripotent adult stem cell migration in vivo in planarians

“…Integrins have conserved roles in orchestrating cell migration, providing a connection between physical actions of the actin cytoskeleton and signaling mechanisms instructing migratory activity (Mogilner and Keren, 2009;Vicente-Manzanares et al, 2009). The recently published regenerative phenotypes for planarian β1-integrin suggested to us that the cellular disorganization observed in these studies could be due to failures in migratory activity (Bonar and Petersen, 2017;Seebeck et al, 2017). We observed that β1-integrin transcript is expressed in dpishowing bands of stem cells (green) and early progeny (magenta) restricted to the irradiationprotected region.…”

“…Using markers of the epidermal lineage we uncover that cells at some stages of differentiation are more migratory than other cells that are at other stages of differentiation. RNAi of Smed-MMPa (mmpa) and of an ortholog of beta-integrin, Smed-β1-integrin (β1-integrin), disrupt cell migration and the formation of extended processes, providing proof of principle for this approach (Bonar and Petersen, 2017;Isolani et al, 2013;Seebeck et al, 2017). Using RNAi we also show that the polarity determinant Smed-notum (notum) is necessary for the homeostatic anterior migration of cells in unwounded animals, but not for cells to form processes or to migrate in response to wounding (Petersen and Reddien, 2011).…”

The Cellular and Molecular Basis for Planarian Regeneration

“…Studying how regeneration ability varies in planarian evolution is an intriguing direction; b-catenin RNAi ''awakened'' the ability to regenerate heads in planarian species that normally do not regenerate heads from posterior amputation planes (Liu et al, 2013;Sikes and Newmark, 2013;Umesono et al, 2013). Stem cell-migratory responses to wounds and organization of cells in regeneration are additional important directions with insights emerging (Abnave et al, 2017;Bonar and Petersen, 2017;Seebeck et al, 2017). Comparison of planarian embryogenesis to regeneration is also an attractive goal (Martín-Durá n et al, 2010; Davies et al, 2017).…”

Substrate elasticity induces quiescence and promotes neurogenesis of primary neural stem cells—A biophysical in vitro model of the physiological cerebral milieu

“…In the CNS, integrins and other transmembrane proteins that bind to the ECM are the main determinants of cellular mechanosensing (Stukel & Willits, ). Interestingly, these molecules are not only known for the mechanical forces they transmit but also for their various biological effects on cells in the brain (Klein et al, ; Seebeck et al, ; Williams, Furness, Walsh, & Doherty, ). Overall, elasticity constitutes an important mechanical factor influencing various cell types in the body, including embryonal stem cells (Chowdhury et al, ; Evans et al, ), mesenchymal stem cells (Engler, Sen, Sweeney, & Discher, ; Schellenberg et al, ), hematopoietic stem cells (Kumar et al, ), or cardiomyocytes (Hersch et al, ).…”