• MIUR - PRIN - PROGETTI DI RICERCA DI INTERESSE NAZIONALE

• PHENIX - From cell fate plasticity to tissue homeostasis to longevity: insights from two emerging model invertebrates, the "immortal jellyfish" Turritopsis dohrnii and the budding ascidian Botryllus schlosseri

Abstract

Our knowledge on the plasticity of cell fate, cell stemness and organismal longevity in mammals is mostly based on in vitro studies. Little information is available on the fundamental nature of stemness, the stability of cell differentiation, and cell reprogramming from in vivo systems. Novel insight may be useful to the study of senescence and the molecular controls of cell differentiation in non-mammalian, underinvestigated models. The hydrozoan "immortal" medusa Turritopsis dohrnii challenges basic aspects of both aging theories and cell reprogramming: life cycle reversal can occur at any stage of medusa growth, including the adult. Reverse development (RD) is actually induced by epigenetic factors as well as by endogenous signals of senescence. This unparalled potential in the animal kingdom is achieved by cell dedifferentiation-redifferentiation and transdifferentiation mechanisms. Differently, the colonial tunicate Botryllus schlosseri weekly exhibits a cyclical, zooid budding rhythm and constitutive generation of the whole colonial body (blastogenesis, BG), with regular reactivation of early development molecular programs, differentiation of pluripotent stem cells, and putative transdifferentiation of adult somatic cells. These extraordinary potentials for regeneration and dedifferentiation represent ideal models to understand how gene regulatory networks and their associated cell behaviors drive ontogeny, the molecular switches of developmental transitions, and the mechanisms controlling the stability of cell fate.

PHENIX aims to shed light on the molecular pathways involved in RD of T. dohrnii and BG of B. schlosseri, focusing on the mechanisms controlling the ontogenetic direction of life cycle, the stability of cell fate, and stem cell renewal. The workplan will embrace transcriptomic, gene expression and morpho-functional  analyses. The comparison of these processes in two evolutionary distant invertebrate models, a cnidarian and a chordate, will ensure the identification of the evolutionarily most conserved genes/pathways underlying theses processes. Transcriptome profiling will be used: (1) in each model species, to identify genes differentially expressed among specific life cycle stages characterized by the occurrence of the above mentioned processes; (2) to identify genes and pathways up- and down-regulated in these processes in both our models.

Among the identified differentially expressed genes, we will focus our attention on: the four Yamanaka's factors (Sox2, Klf4, Oct3/4, cMyc), transcription factors with top reprogramming activity in vertebrates; YAP/TAZ, the regulators of the Hippo signaling pathway; the gap junctions (GJs) machinery. Pharmacological perturbation of cell-cell communications, regeneration-dedifferentiation experiments, morpho-functional analyses and gene expression studies will contribute towards a better understanding of the extraordinary biological phenomena of RD and BG.

• PIRAINO Stefano - Università del SALENTO – unità operativa n.1, Capofila
• GISSI Carmela Università degli Studi di BARI ALDO MORO – unità operativa n.2
• MANNI Lucia - Università degli Studi di PADOVA – unità operativa n.3
• PENNATI Roberta - Università degli Studi di MILANO - unità operativa n.4
• LEONE Antonella - Consiglio Nazionale delle Ricerche - unità operativa n.5