Founder Cell Population Research Articles

Interactions between primordial germ cells play a role in their migration in mouse embryos

Primordial germ cells (PGCs) are the founder cell population of the gametes which form during the sexually mature stage of the life cycle. In the mouse, they arise early in embryogenesis, first becoming visible in the extraembryonic mesoderm, posterior to the primitive streak, at 7.5 days post coitum (d.p.c.). They subsequently become incorporated into the epithelium of the hind gut, from which they emigrate (9.5 d.p.c.) and move first into the dorsal mesentery (10.5 d.p.c.), and then into the genital ridges that lie on the dorsal body wall (11.5 d.p.c.). We have used confocal microscopy to study PGCs stained with an antibody that reacts with a carbohydrate antigen (Stage-Specific Embryonic Antigen-1, SSEA-1) carried on the PGC surface. This allows the study of the whole PGC surface, at different stages of their migration. The appearance of PGCs in tissue sections has given rise to the conventional view that they migrate as individuals, each arriving in turn at the genital ridge. In this paper, we show that PGCs leave the hind gut independently, but then extend long (up to 40 microns) processes, with which they link up to each other to form extensive networks. During the 10.5-11.5 d.p.c. period, these networks of PGCs aggregate into groups of tightly apposed cells in the genital ridges. As this occurs, their processes are lost, and their appearance suggests they are now non-motile. Furthermore, we find that PGCs taken from the dorsal mesentery at 10.5 d.p.c. perform the same sequence of movements in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental potentialities of cells derived from the truncal neural crest in clonal cultures

The developmental potentialities of single truncal neural crest derived cells were analysed in clonal cultures. The clone-forming ability and differentiation potential of crest cells migrating through the somitic mesoderm of 3-day-old embryos (E3) and of non-neuronal cells of dorsal root ganglia taken at E6-14 were compared. Since most of the cells present in the sclerotomal and rostral parts of the somite et E3 become later on incorporated into the spinal ganglia, one can consider that these two cell populations represent the same derivatives of the trunk neural crest at different developmental stages. After 10 days in vitro, the size of clones and their phenotypic composition varied noticeably, revealing a certain heterogeneity in the founder cell populations in terms of developmental potencies. Clones obtained from migrating neural crest cells at E3 were often large (>1000 cells) and many of them contained neuronal and non-neuronal cells. Dorsal root ganglion cells produced mostly small clones (<100 cells) in which only non-neuronal (i.e. glial) phenotypes were expressed. Therefore, both the capacity for proliferation and the differentiation ability of cloned neural crest derived cells decrease considerably with increasing embryonic age. This is even more striking if these results are compared with those obtained previously in our laboratory with single cells cultures of E2 cephalic neural crest. In the latter case, both clone sizes and cellular diversity within the colonies were much higher than with E3 truncal crest and dorsal root ganglia (DRG) non-neuronal cells. The second result of the present work concerns the differentiation of the dormant autonomic neuronal precursors of the DRG. It has been established previously that the non-neuronal cells of the DRG include adrenergic precursors than can differentiate in mass culture of dissociated DRG cells. We show that these cells never differentiate in clonal cultures but depend upon the cell density of the culture. This suggests that cell to cell interaction between crest derived cells are critical in eliciting the differentiation of the adrenergic phenotype.

Towards an understanding of the behaviour of root meristems

The behaviour of cells within the root apex and its meristem is considered within the framework of the following propositions. 1. (1) The quiescent centre is the site of a founder cell population from which all other cells of the root can be derived. During steady-state growth of the root the founder cells progress through the mitotic cycle slowly and have an indeterminate reproductive life-span. 2. (2) Surrounding the quiescent centre are initial cells and their derivatives; both types of cells progress through the mitotic cycle quickly and the derivative cells have a determinate reproductive life-span. The number of founder cells remains approximately constant during root growth, so when such a cell divides one of its daughters, or another founder cell, must displace an initial and take on its function. 3. (3) It is supposed that in the root apex there are gradients of substances that regulate aspects of cellular and nuclear behaviour. Founder cells in the quiescent centre may be the source of a gradient of a substance (perhaps a cytokinin) which, as long as its concentration is at an appropriate level, triggers mitosis and cytokinesis. A second substance (perhaps an auxin) moves towards the quiescent centre from a source in the maturing cells of the root apex; it is supposed that its concentration is appropriate to maintain nuclear DNA synthesis in cells of the meristem and elsewhere in the apex. The relative concentrations of the two substances may regulate the rates of mitosis, cell growth and the switch from mitosis to endomitosis. 4. (4) Besides their role in maintaining cell division in the meristem, the founder cells, together with the cells immediately surrounding them, may constitute a pattern of cells that is self-perpetuating. 5. (5) Founder cells may constitute a pool of cells whose proliferative potential is not impaired by the passage of time. The propositions are predictive and possible experimental tests of, as well as evidence for, their veracity are presented.