In this paper, we review how midbrain and hindbrain are specified. Otx2 and Gbx2 are expressed from the early phase of development, and their expression abuts at the midbrain hindbrain boundary (MHB), where Fgf8 expression is induced, and functions as an organizing molecule for the midbrain and hindbrain. Fgf8 induces En1 and Pax2 expression at the region where Otx2 is expressed to specify midbrain. Fgf8 activates Ras-ERK pathway to specify hindbrain. Downstream of ERK, Pea3 specifies isthmus (rhombomere 0, r0), and Irx2 may specify r1, where the cerebellum is formed.
Fgf8 is induced at the boundary of Otx2 and Gbx2 expression. Fgf8 induces En1/Pax2 expression in the region where Otx2 is expressed to define midbrain. Fgf8 activates Ras-ERK pathway to specify hindbrain. Donstream of ERK, Pea3 specifies r0 (isthmus), and Irx2 specifies r1.