Fig. 7. A model for the early regionalization of the chick anterior neural plate. During HH4-6, a system that involves Otx2 and Gbx2 sets up domains and a boundary corresponding to the prospective mid-hindbrain boundary where the isthmic organizer (isO) develops (A) (Broccoli et al., 1999; Millet et al., 1999; Katahira et al., 2000). At around the same time, mutual repression between Irx3 and Six3 positions a boundary within the prospective forebrain, which later coincides with the ZLI (B). Slightly later, mutual repression between Pax6 and Pax2/En1 defines an intermediate boundary between the above two that corresponds to the dien-mesencephalic boundary (C) (Matsunaga et al., 2000). As these systems function independently, the early anterior neural plate accordingly acquires three boundaries at different anterior-posterior levels, being subdivided into four discrete domains potentially by a combinatorial code of transcription factors (D). Subsequently, localized signals produced from various signaling centers (e.g. anr, isO, pcp, nc) create fields of distinct histogenetic properties (e.g. te, ht, ot, ce; E). The longitudinal axes of the neural plate and tube are indicated by red arrows. anr, anterior neural ridge; ce, cerebellum; di-mes, dien-mesencephalic boundary; ht, hypothalamus; isO, isthmic organizer; nc, notochord; ot, optic tectum; pcp, prechordal plate; te, telencephalon; zli, zona limitans intrathalamica.