Specification of the meso-isthmo-cerebellar region: The Otx2/Gbx2 boundary

The midbrain/hindbrain (MH) territory containing the mesencephalic and isthmocerebellar primordial is characterized by the expression of several families of regulatory genes including transcription factors (Otx, Gbx, En, and Pax) and signaling molecules (Fgf and Wnt). At earlier stages of avian neural tube, those genes present a dynamic expression pattern and only at HH18-20 onwards, when the mesencephalic/metencephalic constriction is coincident with the Otx2/Gbx2 boundary, their expression domains become more defined. This review summarizes experimental data concerning the genetic mechanisms involved in the specification of the midbrain/hindbrain territory emphasizing the chick/quail chimeric experiments leading to the discovery of a secondary isthmic organizer. Otx2 and Gbx2 co-regulation could determine the precise location of the MH boundary and involved in the inductive events characteristic of the isthmic organizer center.