The role of APC/CFZR-1 in the functionality of the gonad of Caenorhabditis elegans

Abstract

Tesis llevada a cabo para conseguir el grado de Doctor por la Universidad de Salamanca.--2020-11-13Proper coordination between the cell division and the differentiation is essential during the development of organisms. The cell-cycle machinery determines during the G1 phase, whether a cell differentiates or continues dividing to achieve this coordination. Many components of the cell cycle active in G1 can act directly on differentiation factors. Among these cell-cycle components highlights the E3 ubiquitin ligase APC/CCdh1 due to its emergent role in the degradation of several differentiation factors. Caenorhabditis elegans constitutes and excellent system to study the possible roles of APC/CCdh1/FZR-1 beyond cell cycle. Previous results from our laboratory demonstrated that APC/CFZR-1 sends to degradation the histone methyltransferase (HMT) MES-4. In this thesis, we have discovered that MES3, a subunit of HMT Polycomb, is also targeted by APC/CFZR-1 . We have observed that the low fertility levels associated with a version of MES-3 not recognizable by APC/CFZR-1 are counteracted in combination with a version of MES-4 not degraded through APC/CFZR-1 . The post-translational and simultaneous regulation of MES-4 and MES-3 through APC/CFZR-1 constitutes a critical mechanism to ensure germline functionality. On the other hand, we have explored the role of APC/CFZR-1 during C. elegans development. We have obtained the first null-allele of fzr-1 described so far. APC/CFZR-1 participates in the development of the somatic gonad, an organ that supports germline development. Specifically, APC/CFZR-1 is necessary for the production of the Distal tip Cell (DTC), a stem-cell niche that maintains a pool of germ cells and leads the outgrowth of the gonad, Absence of FZR-1 makes that cells committed to being DTCs, acquire the SS precursor fate of sister cells. However, an allele of fzr-1 supposed to be constitutively active yields extra DTCs. Both results suggest that APC/CFZR-1 is part of a balance during the fate choice decision 'DTC-SS' in the somatic gonad.Peer reviewe