The quest of modern developmental biology is a detailed molecular description of the process that leads from a fertilized egg to a highly differentiated adult organism containing hundreds of different cell types. Molecular insight into the developmental blueprint not only helps to understand this fundamental biological problem, but provides also strategies and tools to manipulate cells. Our model system to address these questions is the African clawed frog Xenopus, in which nuclear reprogramming of somatic cells had been originally pioneered (see www.xenbase.org). Among its many advantages, we appreciate its ease of manipulation, the availibility of primary embryonic stem cells, and the unique possibility to combine embryological and reverse genetics approaches with biochemical analyses of virtually every developmental stage.
Cellular differentiation is tightly coupled to embryonic patterning and controlled largely on the level of zygotic gene expression, which commences in Xenopus at the midblastula stage. Stable heritable cell fates are established in naive embryonic stem cells by an interplay of signalling pathways (“induction”) and cell-intrinsic properties (“competence”). We investigate the hypothesis that changes in chromatin structure and composition define distinct states of cellular competence that constrain inductive processes and propell development in a directional manner. Over the years, this hypothesis has led us to seminal observations on specific developmental functions for H1 linker histones, ATP-dependent chromating remodelling machines, and histone modifying enzymes. Currently, a major focus lies on the analysis of stage-specific histone modification profiles, which impact embryonic stem cell behaviour and cell differentiation.