Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells.

Cajal-Retzius (CR) cells play a key role in the formation of the cerebral cortex. These pioneer neurons are distributed throughout the cortical marginal zone in distinct graded distributions. Fate mapping and cell lineage tracing studies have recently shown that CR cells arise from restricted domains of the pallial ventricular zone, which are associated with signalling centres involved in the early regionalisation of the telencephalic vesicles. In this study, we identified a subpopulation of CR cells in the rostral telencephalon that expresses Er81, a downstream target of Fgf8 signalling. We investigated the role of the rostral telencephalic patterning centre, which secretes FGF molecules, in the specification of these cells. Using pharmacological inhibitors and genetic inactivation of Fgf8, we showed that production of Fgf8 by the rostral telencephalic signalling centre is required for the specification of the Er81+ CR cell population. Moreover, the analysis of Fgf8 gain-of-function in cultivated mouse embryos and of Emx2 and Gli3 mutant embryos revealed that ectopic Fgf8 signalling promotes the generation of CR cells with a rostral phenotype from the dorsal pallium. These data showed that Fgf8 signalling is both required and sufficient to induce rostral CR cells. Together, our results shed light on the mechanisms specifying rostral CR cells and further emphasise the crucial role of telencephalic signalling centres in the generation of distinct CR cell populations.