Graded Levels of FGF Protein Span the Midbrain and Can Instruct Graded Induction and Repression of Neural Mapping Labels

Graded guidance labels are widely used in neural map formation, but it is not well understood which potential strategy leads to their graded expression. In midbrain tectal map development, FGFs can induce an entire midbrain, but their protein distribution is unclear, nor is it known whether they may act instructively to produce graded gene expression. Using a receptor-alkaline phosphatase fusion probe, we find a long-range posterior > anterior FGF protein gradient spanning the midbrain. Heparan sulfate proteoglycan (HSPG) is required for this gradient. To test whether graded FGF concentrations can instruct graded gene expression, a quantitative tectal explant assay was developed. Engrailed-2 and ephrin-As, normally in posterior > anterior tectal gradients, showed graded upregulation. Moreover, EphAs, normally in anterior > posterior countergradients, showed coordinately graded downregulation. These results provide a mechanism to establish graded mapping labels and more generally provide a developmental strategy to coordinately induce a structure and pattern its cell properties in gradients.