Neural crest progenitors of the melanocyte lineage: coat colour patterns revisited.

Neural crest-derived melanoblasts are the progenitors of melanocytes, the pigment cells of the skin, hair and choroid. Previous studies of adult chimaeric mice carrying different coat colour markers have suggested that the total melanocyte population is derived from a small number of melanoblast progenitors, each of which generates a discrete unilateral transverse band of colour. This work also suggested minimal mixing of cells between clones. We have used two complementary approaches to assess the behaviour of migrating clones of melanoblasts directly in the developing embryo. First, we made aggregation chimaeras between transgenic Dct-lacZ and non-transgenic embryos, in which lacZ is a marker for melanoblasts. Second, we generated transgenic mice carrying a modified lacZ reporter construct containing a 289 base pair duplication (laacZ) under the control of the Dct promoter. The laacZ transgene is normally inactive, but reverts to wild-type lacZ at low frequency, labelling a cell and all of its progeny at random. Mosaic embryos containing labelled melanoblast clones were generated. In contrast to previous data, chimaeric and mosaic embryonic melanoblast patterns suggest that: (1) there is a large number of melanoblast progenitors; (2) there is a pool of melanoblasts in the cervical region; (3) different cell dispersion mechanisms may operate in the head and trunk regions; and (4) there is extensive axial mixing between clones.

Widespread tangential dispersion and extensive cell death during early neurogenesis in the mouse neocortex.

The development of the mammalian neocortex requires radial and tangential migration of cells. Radial migration of differentiated neurons from the ventricular zone (VZ) is well established. It is hypothesised that an earlier phase of tangential migration of mitotically active cells lays down a widespread periodically spaced set of progenitors that generate radial arrays of postmitotic neurons. We use a transgenic cell lineage marker to label and observe the behaviour of progenitors before and during the early stages of neurogenesis. Using optical projection tomography (OPT), we show that individual progenitor cells generate many radially arrayed columns of periodically spaced cells. Column positions indicate the paths taken by these progenitor cells as they migrate, often over long distances, through the proliferative zone. Clonally related cells can be distributed in both hemispheres, suggesting progenitor cells cross the midline in the anterior neural plate. We observe a dramatic and rapid decline in the number of labelled clones after E13.5, indicating that there is extensive cell death at this time.