CELLULAR PATTERNING · Clonal analysis of the progenitors for the mouse anteroposterior axis and adult muscle
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-09-01 → 2007-08-31
- EU contribution
- €150,804
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - CELLULAR PATTERNING (Clonal analysis of the progenitors for the mouse anteroposterior axis and adult muscle)
Embryogenesis involves the successive segregations of distinct cell populations organised initially into broad cellular domains and progressively into the definitive tissues made up of specialised cell types. During adult life, certain developmental processes persist to provide growth and homeostasis of the mature tissues. Understanding of these processes requires information on cell behaviour at clonal level throughout embryogenesis and adulthood. In mammals, the study of cellular patterning and lineage segregations has been hampered by the inaccessibility of the post-implantation embryo and the dearth of single cell labelling methods. To overcome these limitations we developed two novel systems for clonal analysis that allowed for long-term tracing of cell descendants via the expression of heritable lineage markers activated in a precursor cell either randomly or in a spatio-temporally controlled manner. We used these approaches to investigate the genealogical relationships between embryonic lineages and study the behaviour of cells during elongation of the rostrocaudal (head-tail) axis in the mouse embryo. The obtained clonal patterns suggested that surface ectoderm (skin progenitors) and endoderm (e.g. gut, lung) lineages segregated early, before embryonic day (E) 7.5. In contrast, common precursors for neural (central nervous system) and mesodermal (e.g. muscle, bone, kidney) tissues were still present at mid-gestation (E 10.5). These bipotent precursors presented self-renewing characteristics and could contribute descendants dispersed extensively in both trunk and tail, demonstrating the existence of clonal continuity in the axis and by that, a continuity of cellular operations used throughout axial elongation. However, a proportion of the clones to which these self-renewing precursors gave rise, did not extend up to the posterior end of the embryo, suggesting an exit from the progenitor pool before the end of axial elongation. This exit could denote a progressive depletion of precursors that underlay the imminent arrest of axis elongation at E 13.5.
Data: CORDIS, © European Union
Project objective
Embryonic development occurs via successive lineage segregations leading to the progressive compartmentalisation of a pluripotent embryonic primordium into broad cellular domains and eventually into specific tissue types. Over the last decades, an abundance of information has been gained into the genetic and molecular regulation of theses processes, while little is still known concerning the cellular aspects of development. The purpose of the proposed work is to provide a better insight into cellular behaviour responsible for tissue diversification and patterning along the anteroposterior axis by addressing previously unresolved questions relating to the genealogical relationships of distinct cell populations, the unipotent or multi-potent nature of their pro genitors and the existence of clonal continuity between different axial domains.It also aims to examine the relationship between these early patterning events and the development of adult muscle during secondary myogenesis. Information derived on these is sues will have significant implications for future healthcare strategies and the development of cell therapies in particular for muscle degenerative diseases. The project will take advantage of a recently developed approach for retrospective lineage analysis which is clonal, non-invasive, non-biased in respect to the cell initially labelled, and allows visualisation of a clone at any time after its initiation. Thus, this approach is the only suitable for providing a definitive answer to the genealogical relationships of cells and for describing cellular behaviour throughout development. Implementation of the project will complement the researcher's previous experience and thus contribute to her training towards professional independence. The mobility will be beneficial to the transfer of competencies between European countries and in particular to the development of research activity in Greece in the future.
Original text from CORDIS.
Participants
- INSTITUT PASTEUR · PARISCoordinatorFrance
Links
Data: CORDIS, © European Union