Kristine A. Henningfeld
Group leaderDept. of Developmental Biochemistry
Abteilung Entwicklungsbiochemie Justus-von-Liebig-Weg 11
Major Research Interests Throughout embryogenesis, multiple regulators act in a concerted manner to control the competence, differentiation and maturation of individual cells. During the development of the nervous system, ectodermal cells first acquire a neural fate, and individual cells are subsequently selected to undergo differentiation. The competence of the neural precursor cells to differentiate changes over time, thereby giving rise to the broad cellular diversity that exists in the CNS. To ensure that the proper number of individual cell types is generated, it is imperative for the process of differentiation to be highly regulated. It is anticipated that the hierarchy of events, which may allow for a directed differentiation of adult or embryonic stem cells in vitro, recapitulates those events that occur during embryogenesis. The elucidation of the molecular basis of neural developmental processes is therefore essential for such cell-based approaches that will eventually aim at the treatment of neuronal dysfunction. We study the earliest events of vertebrate neurogenesis using the frog Xenopus laevis as a model system. Xenopus has proven itself as a valuable model system to elucidate the cascade of events that controls early neurogenesis owing to simplicity and accessibility of primary neurogenesis. In Xenopus, the first neurons, termed primary neurons, are born within the induced neuroectoderm shortly after gastrulation in three bilateral longitudinal domains. The differentiation of the primary neurons is driven by proneural bHLH transcription factors, such as neurogenin2 (Ngn2), which induces later acting genes required for withdrawal of the progenitor cells from the cell cycle and terminal differentiation. Cell-cell signaling mediated by the Notch pathway restricts the number of neurons that are generated at this time. Our research is focused on the identification and characterization of the intrinsic factors and signaling pathways that governs the early determination, differentiation and subtype specification of vertebrate neurons.