ELSEVIER PI1 SOS90-6238(96)00214-6 Reproductive Toxicology, Vol. 11, Nos. 213, pp. 317-319, 1997 Copyright 0 1997 Elsevier Science Inc. Printed in the USA. All rights reserved 0890.6238/97 $17.00 + .OO NIEHUEPA WORKSHOPS CELL LINEAGES zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO JANET ROSSANT,* VIRGINIA E. PAPAIOANNOU,~- KIRSTIE LAWSON,* SCOTT FRASER,~ and ANDREW COPP~I *Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada i-Columbia University, Department of Genetics and Development, New York, New York $Netherlands Institute for Developmental Biology, Hubrecht Laboratorium, Utrecht, The Netherlands QCalifomia Institute of Technology, Pasadena, California IlInstitute of Child Health, University of London, London, UK CELL LINEAGE WORKSHOP ma1 programmed cell death was also discussed. Dr. Copp reviewed interactions between genetic predisposition and environment in various models of developmental defects. In this workshop, we considered the normal cell lineage relationships in the early mouse embryo and discussed how further knowledge of such relationships could assist in understanding the effect of environmental perturba- tions on development. We focused on events in the un- disturbed embryo and how to use cellular and molecular approaches to understand the processes of lineage devel- opment and pattern formation. Dr. Lawson reviewed our current understanding of the fate map of the gastrulating mouse embryo, an important prerequisite for all other analysis of normal or abnormal development. Dr. Fraser discussed the various techniques that can be applied to tracing lineage relationships. With some of the current powerful lineage techniques, it may be possible to reas- sess the effects of developmental toxicants and relate them to known developmental pathways. Another impor- tant tool in our understanding of normal development is the expression analysis of developmentally regulated genes. Dr. Martin and Dr. Rossant described some stud- ies on genes expressed around the time of gastrulation that illustrate how expression domains can both act as useful molecular markers of development and give clues as to the function of specific genes in developmental processes. Again, use of such markers will enable clearer understanding of developmental and genetic defects. Programmed cell death is an important component of normal developmental processes and is often associated with developmental defects as well. The issue of whether teratogen-induced cell death can be an extension of nor- Participants: Nigel Brown, John DeSesso, Lewis Holmes, Roger Pedersen, Frank Welch, Phil M. Iannaconne. Address correspondence to: Janet Rossant, Ph.D., Samuel Lunen- feld Research Institute, Mt. Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5 Canada. Following each presentation, a designated discus- sant outlined the implications for developmental toxicol- ogy and teratology. Those discussion points have been incorporated in the summary of the general discussion that followed the scientific presentations. OVERVIEW AND CONCLUSIONS Cell lineage analysis Studies on cell lineage allocation in the early post- implantation mouse embryo have illustrated again the likely evolutionary conservation of developmental mechanisms across vertebrate species (Lawson & Peder- son, 1992a,b; Lawson et al. 1991). This indicates the possibility of using information from other species to formulate hypotheses about lineage allocation and com- mitment in mammals. It should be borne in mind that the presence of a reproducible fate map does not preclude the existence of developmental plasticity or provide any direct evidence on the relative importance of intrinsic cell determinants and extrinsic cellular interactions in determining cell fate. The fate map of the gastrulating mouse embryo is not a map of cell commitment; the potential of cells in different regions can only be as- sessed by experimental perturbations. Even beyond the point at which cells have been allocated to a specific organ rudiment, there may be considerable compensatory capacity due to recruitment of uncommitted cells or the presence of stem cells in the organ rudiment. Critical periods of sensitivity to toxic agents may reflect the timing of allocation to organ anlage, and the extent of compensatory mechanisms may affect the dif- ferential sensitivity of different embryonic stages and tissue types. To understand the results of exposure to 317