INDUCTIVE INTERACTIONS DIRECT EARLY REGIONALIZATION OF THE MOUSE FOREBRAIN

The cellular and molecular mechanisms that regulate regional specifica tion of the forebrain are largely unknown, We studied the expression o f transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-late ral and local patterning of the prosencephalic neural plate, Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ect oderm and bone morphogenetic proteins, This suggests that the forebrai n employs the same medial-lateral (ventral-dorsal) patterning mechanis ms present in the rest of the central nervous system, We have also fou nd that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning, The anterior neural ridge is essential for expression of BF1, a gene encoding a transcript ion factor required for regionalization and growth of the telencephali c and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, sugges ting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate i s subdivided into distinct anterior-posterior domains that have differ ent responses to the inductive signals from the prechordal plate, Soni c Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior pat terning creates transverse zones with differential competence within t he neural plate, (2) patterning along the medial-lateral axis generate s longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define th e regional organization.