CORDIS - EU research results

Clonal analysis of the progenitors for the mouse anteroposterior axis and adult muscle

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.