Return to main Teaching Tools page for Martin Raff >>
- The growth hormone (GH)/ IGF1 endocrine system is a major stimulator of mammalian growth: without treatment, babies that are unable to make GH end up as midgets, while those that produce excessive amounts of GH end up as giants. Could differences in this endocrine system account for why humans grow to be so much larger than mice?
- Since the growth of a cell depends on extracellular growth factors produced by other cells, is it likely that differences in the concentrations of such growth factors explain why some cell types in your body (such as skeletal muscle cells) are very large, while other cell types (such as lymphocytes) are very small?
- Most of your cells are said to be diploid because they contain two complete sets of chromosomes, one set inherited from your mother and one set from your father. A general finding is that cell size increases with increasing ploidy: for example, tetraploid cells, which contain four complete sets of chromosomes, are about twice the size of diploid cells of the same kind. Can you think of reasons why cell size increases with increasing ploidy?
- What does the drug aphidicolin do, and why is it useful for studying the growth (enlargement) of cells in culture?
- Surprisingly, aphidicolin-arrested Schwann cells that are stimulated to grow by the growth factors present in FCS grow at a rate that is independent of cell size—that is, little cells and big cells add the same amount of protein or volume per day. Yeast cells arrested in S phase because of a mutation in a gene required for DNA replication also continue to grow when cultured in optimal nutrients. But, in contrast to aphidicolin-arrested Schwann cells (which are also arrested in S phase), the mutant yeast cells grow progressively faster as they increase in size. Can you suggest a possible explanation for this difference between the aphidicolin-arrested Schwann cells and the arrested mutant yeast cells, assuming that the difference is not caused by the different ways that the cells have been arrested in S phase?
- Cancer results when a cell and its progeny accumulate mutations that give the cells a proliferative advantage over their normal neighbors, causing an abnormally large accumulation of the mutant cells, called a tumor. Is an abnormal cell division rate sufficient to explain the development of cancer?
- It has been proposed that proliferating cells have cell-size checkpoints in their cell division cycle, where the cell can pause and assess whether it is large enough to proceed to the next step in the cycle, thereby ensuring that the cell divides at an appropriate size. One reason for thinking that proliferating cells must have such checkpoints is that the two daughter cells produced by a cell division are not always exactly the same size. If the bigger daughter cell were to grow faster than the smaller daughter cell, as intuitively one might expect, the size differences would be expected to get greater and greater over time, as the larger daughters would produce still larger daughters, which would then grow even faster. Yet, it is observed, for various proliferating cell populations in culture, that the distribution of cell sizes remains constant over weeks and months, suggesting that cells have cell-size checkpoints that allow the smaller daughter cells extra time to grow before they divide. But, we have seen that for aphidicolin-arrested Schwann cells, big cells grow no faster than small cells. If this were also the case for untreated, normally proliferating Schwann cells, and big and small proliferating Schwann cells were to grow and progress through the cell cycle at the same rate, would they need cell-size checkpoints to maintain a constant distribution of sizes as they proliferate?
- Because large yeast cells seem to grow faster than small yeast cells (at least when blocked in S phase), it has been proposed that proliferating yeast cells have cell-size checkpoints that help them maintain their appropriate size. It has been shown that yeast cells divide at a size that is characteristic for a particular culture medium—in general, the more nutrient rich the medium, the larger the cell size at division. Moreover, when, switched from a nutrient-poor medium to a nutrient-rich medium, yeast cells rapidly adjust (within one division cycle) and start dividing at the larger size that is appropriate for the nutrient-rich medium. What does this latter finding imply about the nature of the postulated cell-size checkpoint mechanism?
- When Schwann cells proliferate in serum-free medium containing optimal concentrations of IGF1 and GGF, their average size is less than half that of cells proliferating in medium containing FCS, without added IGF1 or GGF. The cells proliferate at roughly the same rate in the two conditions, and they maintain their characteristic cell size distributions over time. What do these findings imply about the FCS?
- As mentioned in Question 8, when yeast cells are switched from a nutrient-poor medium to a nutrient-rich one, the cells rapidly adjust within one division cycle and start dividing at the larger size that is appropriate for the new medium. By contrast, however, when proliferating Schwann cells are switched from a serum-free medium containing IGF1 and GGF to a medium containing FCS, it takes about six divisions and about ten days before they acquire the larger average size of Schwann cells proliferating in FCS from the start. Can you explain why yeast cells and Schwann cells behave so differently in such switch experiments?