Extensive morphogenetic cell movements play a central role in the embryonic development of higher organisms. In spite of significant progress in the past years it is still not clear how these movements are regulated.The classical view states that cells are put in C. elegans in place by cell division. Our recent results demonstrate that active cell movements sort the descendants of the blastomeres present at the 12-cell stage (Figure A) into discrete regions (Figure B), thus making C. elegans a suitable system for the analysis of cell migrations. Using the recently-developed 4-dimensional microscopy (see link to homepage) it is possible to analyse the movements of all cells in the embryo in detail. Furthermore, C. elegans embryos offer several technical advantages including the ability to alter development micromanipulation and by both forward and reverse genetics. All molecular analyses are greatly facilitated by the recently completed genome project.

First results

1. If one changes the identity of early blastomeres (genetically or by preventing interactions) so that e.g. the ABalp cell adopts the fate of ABarp, the progeny of this blastomere will migrate from an ectopic position in the embryo to a position typical of the acquired fate (Figure C). Therefore, cell movements are coupled to cell fate and there must be a coordinate system in the embryo.

2. By laser ablation or removal of different early blastomeres, and by changing the identity of most early blastomere fates, it was shown that neither single guiding posts nor local cell-cell interactions seem to be solely responsible for pathfinding in the embryo. The key question of this project is therefore: How are cells actually guided?

Prospects

- By analysing mutants which cause a failure in pathfinding, we plan to identify genes involved in the control of cell movement. This analysis will be done using 4-dimensional microscopy on an extensive collection of maternal-effect lethal mutants which were isolated in my lab. Thanks to the genome project it has become relatively easy to do a molecular analysis of the identified genes.

- Further manipulations (blastomere removal and laser ablation experiments) will be used to study the basic principles of morphogenetic movements, as it has become clear that identification of involved genes alone may not be sufficient to reach a deeper understanding of the process being studied.