About This Project

Embryonic cells make choices that guide the differentiation of their clonal descendants. Such decisions establish the outline of a snail's whole body in a spatially patterned array of just twelve diverse, unambiguously identified single cells which are differentially exposed to a signal briefly emanating from a point source. We want to know if (and how) a change in this pattern causes the neck-founder cells to inappropriately form trunk structures, and if lack of a neck makes the head pop off.

Ask the Scientists

What is the context of this research?

How do embryonic cells decide to form various body regions, organs and tissues? Snail embryos build the body almost entirely from thirteen (easily recognizable and accessible) regional founder cells that are formed during the first few hours of development. Single-cell deletion experiments indicate that at these early stages, each cell becomes determined to form a certain body region. These decisions depend on cell-intrinsic factors in combination with an intercellular signal. In an unpublished experiment, removal of the right-hand body quadrant founder cell often leads surprisingly to development of a perfect trunk and a small, detached head. Why? We hypothesize that cell-intrinsic factors are acting normally in this situation, but the distribution of intercellular signal is altered.

What is the significance of this project?

Importantly, this study analyzes development by focusing on unique single cells with well-defined neighbor relationships and precisely predictable behaviors over time. We hypothesize that after early loss of the right-hand body quadrant founder cell, some remaining cells are abnormally exposed to an intercellular signal triggering ERK activation, and consequently adopt the right-hand quadrant fate. Another question: why does the head pop off? We hypothesize that cells inappropriately activating ERK (and forming trunk structures) are diverted from a 'neck' fate that normally plays a role in keeping the head attached. Defining the 'positional value' of each founder cell in an alternative situation, and connecting this with altered cell fates, will help define the elements of this system.

What are the goals of the project?

The basic experiment - ablation of one of the embryo's four quadrant-founder cells - was done a long time ago (Clement, 1956: J Exp Zool 132: 427-446), but the results were never reported. We have repeated this experiment and obtained reproducible results. Now we have three goals for further analysis. The first is clonal fate mapping, where a fluorescent dye injected into a single cell is inherited by descendant cells, showing what tissues and organs develop from the injected cell. Second, we want to analyze ERK activation at the single-cell level in early embryos, to test the idea that intercellular signaling is altered in three-quarter embryos. Third, we want to visualize molecular markers of early and later developmental pathways in the experimentally altered embryos.