EvoCellFate · Evolution of cell fate decision during development

Evolution of cell fate decision during development

Understanding the mechanisms underlying phenotypic diversification in evolution is a central challenge in modern biology. To understand the basis of biodiversity, we need to know how molecular and genetic processes control development and shape phenotypic evolution. A key consequence of the architecture of developmental mechanisms is to constraint and biases the evolutionary process, thus shaping the evolution of morphological diversity and possibly producing different evolutionary trajectories in different taxa (evolutionary trends;1,2). The mutational process generates molecular variation that influences phenotypic variation through the genotype-phenotype map, and this phenotypic variation is then subjected to selection and drift. Importantly, even if mutation is random at the genotype level (in first approximation), it does not necessarily result in isotropic exploration of phenotype space. Therefore, understanding the mutationally accessible phenotypic spectrum (mutational variance) is central to investigating the possible evolutionary routes of phenotypic change. The nematode vulva is ideal to study the evolution of developmental mechanisms because of its defined and homologous cellular framework, its particularly well-understood developmental system, the fast development of C. elegans (a generation in 3 days) and the known nematode diversity (3, 4). Nematode vulva development occurs from a subset of six ventral epidermal blast cells, named P3.p to P8.p. The pattern of vulva cell fates is conserved and invariant within the Caenorhabditis genus, except for P3.p that can adopt two different fates that are highly variable within and between species. The fast evolution of P3.p fate matches the mutational variance properties of this cell when the organism is subjected to random mutation in the laboratory(7). In contrast, the Oscheius genus of nematodes displays a completely different pattern of natural variation in cell lineages during vulva development(5). In Oscheius, the P3.p cell has an almost invariant cell fate, and the patterns of cell division of P4.p and P8.p are highly polymorphic between and within Oscheius species. How do the natural patterns of evolution of homologous cells become so distinct between nematode genera? The project is organized in two main objectives. The first objective was to identify the genetic and molecular elements that cause high mutational variance of P3.p cell fate variation in two Caenorhabditis species and to identify the genetic basis of natural variation in P3.p cell fate decision between wild isolates of C. elegans. The second objective was to investigate whether biases in developmental mutability could be the basis for the evolution of evolutionary trends between different genera. The topic of cell fate decision in stem cell biology(9) and developmental biology(10) has been highly investigated. However, the role of spontaneous mutations and natural genetic variation in cell fate decision has been largely dismissed. Additionally, this question is not just relevant for the field of evolution of development, but fundamental to understand the role of human genetic diversity in diseases such as cancer(11).

Data: CORDIS, © European Union