© 1990 SAMiller

An organismal view of the patterns of processes such as cell division and cell death can provide context for emerging details of molecular processes in developing systems. Providing these fundamentals about populations of developing cells has been one of the long-term projects of my laboratory. Some very talented undergraduate students have contributed to the work as they have learned more about development and doing science.

We have used thymidine autoradiography along with BrdU and TUNEL immunocytochemistry on our library of serial sections from a variety of stages of chick and mouse embryos to analyze potential contributions of cell division and cell death (apoptosis) in the creation of early form (morphogenesis).

Localized high proportions of cell division adjacent to areas of significantly lower proliferation suggest that differential growth has as role in producing the folds and tubes that shape gut, body, and amnion, and in rupture of chick oral membrane and closing plates. These patterns suggest hinged folding of endoderm to form the gut tube in chicks and mice. Interesting asymmetries of cell proliferation occur in 8-day mouse embryos that are closing body tubes as they rotate about their axis. Ectoderm shows a L>R asymmetry in normal mice, and inverse asymmetries exist in ectoderm of rotating situs inversus mice. An opposing asymmetry in normal mouse endoderm may help drive axial rotation.

Proliferative differentials might also reflect domains of genetic activity. Our maps of patterns of cell proliferation will be fundamental to interpreting actions of genes, which can now be marked in situ.

Localized removal of cells is another reflection of genetic activity that can also be significant during morphogenesis. Work in my lab has shown that programmed cell death (PCD), also known as apoptosis, is involved in a variety of developmental events. PCD removes an unnecessary tail gut and remnants of the chick primitive streak, remodels chick cloaca, fenestrates chick cloacal membrane and occluded rectal cord and may have a minor role in removal of pharyngeal membranes. Localized PCD sculpts rudiments of natal down feathers and is abundant in cells of the ephemeral periderm as it is being shed on the 18th day of incubation. Apoptotic markers suggest PCD is involved in cavitation of mammalian, but not avian, middle ear space. Location of marked cells suggests that PCD helps remove aortic arch arteries in chick embryos.

The possibility that apoptosis is also involved in removal of the thyroglossal duct, remodeling of early chick thryoid rudiments and removal of ventral cardiac mesentery has been a subject of investigation by several students. Results will be posted when data are sufficient.

A single mechanism is rarely an explanation for any event in biology, so it is unlikely that cell division or cell death alone account exclusively for these developmental phenomena. However, the contributions of these cellular actions have been overlooked by many investigators, and these data provide essential context for the emerging data on molecular genetic activity during early morphogenesis.