Figure 6. Wnt1 and Fgf8 signaling establishes a gene regulatory network to control the induction and maintenance of the midbrain-hindbrain boundary (MHB).

A positive regulatory loop established by the reciprocal expression of Wnt1, En1/2, and Fgf8 is responsible for establishing and maintaining the MHB. Concomitantly, mutual activation of Fgf8 and Gbx2 establishes anterior hindbrain (i.e. metencephalic) cell identities posterior to the MHB whereas mutual repression of Fgf8 and Otx2 induces midbrain cell fates anterior to the MHB. Reciprocal Otx2 and Gbx2 repression is also critical in establishing these cell types at the MHB.