The research of the group aims at investigating the molecular network that underlies the initial steps of nervous system development in vertebrate embryos. In recent years, significant progress has been made in elucidating the signals that are involved. An important realization was that the inductive events are regulated by a small set of cell-cell signaling pathways that are integrated in the embryo and trigger distinct cell fate changes and morphogenetic responses.
With its large egg size, high number of embryos, and rapid external development, the frog Xenopus laevis provides a favorable model system for the study of signaling events. We developed a novel method designated secretion cloning that allowed the isolation of secreted proteins as full-length cDNA clones, which could be directly used for functional characterization in mRNA microinjection experiments (Pera and De Robertis, Mech. Dev., 2000; Pera et al., Int. J. Dev. Biol., 2005).
We introduced an active role for Insulin-like growth factors (IGFs) in head and neural induction (Pera et al., Dev. Cell, 2001). A common mechanism was described to integrate IGF, Fibroblast growth factor (FGF) and Bone morphogenetic protein (BMP) signals via phosphorylation of Smad1 in neural induction (Pera et al., Genes Dev., 2003).
More recently, we presented the secreted serine protease xHtrA1 as positive feedback regulator of FGF signaling. xHtrA1 mobilizes latent FGF-proteoglycan complexes that act as long-range signals during specification of the primary body axis, mesoderm induction, and neuronal differentiation (Hou et al., Dev. Cell, 2007).
We also decribed a role of Retinol Dehydrogenase 10 (XRDH10) as feedback regulator for retinoic acid signaling during embryonic pattern formation and regionalization of the neural tube. We suggest that the combinatorial gene expression and concerted action of XRDH10 and other enzymes involved in the conversion of Vitamin A into retinoic acid constitute a “biosynthetic enzyme code” for the establishment of a morphogen gradient (Strate et al., Development 2009).
Our aim is to understand, how key inductive signals interconnect and are regulated during neural development. To this end, we apply molecular and biochemical techniques in Xenopus, complemented by genetic studies in the mouse. The mechanisms that determine cell fate in the developing nervous system are re-used in other aspects of development, and basic principles of cellular signalling are conserved across species.
The findings made in vertebrate models can be extended to mammalian stem cells with the perspective to deliver concepts for cell therapeutic applications and the repair of CNS injuries in human.