FGF regulated gene-expression and neuronal differentiation in the developing midbrain–hindbrain region

Abstract

The neuroectodermal tissue close to the midbrain–hindbrain boundary (MHB) is an important secondary organizer in the developing neural tube. This so-called isthmic organizer (IsO) secretes signaling molecules, such as fibroblast growth factors (FGFs), which regulate cellular survival, patterning and proliferation in the midbrain and rhombomere 1 (R1) of the hindbrain. We have previously shown that FGF-receptor 1 (FGFR1) is required for the normal development of this brain region in the mouse embryo. Here, we have compared the gene expression profiles of midbrain–R1 tissues from wild-type embryos and conditional Fgfr1 mutants, in which FGFR1 is inactivated in the midbrain and R1. Loss of Fgfr1 results in the downregulation of several genes expressed close to the midbrain–hindbrain boundary and in the disappearance of gene expression gradients in the midbrain and anterior hindbrain. Our screen identified several previously uncharacterized genes which may participate in the development of midbrain–R1 region. Our results also show altered neurogenesis in the midbrain and R1 of the Fgfr1 mutants. Interestingly, the neuronal progenitors in midbrain and R1 show different responses to the loss of signaling through FGFR1.