Insights into the molecular mechanisms underlying neural development in ver
tebrates come from the cloning and the functional analysis of genes which a
re involved in the molecular pathways leading to neural induction, tissue s
pecification and regionalisation of the brain. Among them, transcription fa
ctors belonging to the orthodenticle family (Otx1, Otx2) play an important
role during early and later events required for proper brain development. T
o better understand their functions, several mouse mutants have been genera
ted by homologous recombination. Their analysis clearly indicates that Otx1
is involved in corticogenesis, sense organ development and pituitary funct
ions, while Otx2 is necessary earlier in development, for the correct anter
ior neural plate specification and organisation of the primitive streak. A
molecular mechanism depending on a precise threshold of OTX proteins is nec
essary for the correct positioning of the isthmic region and for anterior b
rain patterning. Finally, vertebrate Otx genes share functional equivalence
with the Drosophila homologue otd, indicating that the genetic mechanisms
underlying pattern formation in insect and mammalian brain development are
evolutionarily conserved. (C) 2000 Elsevier Science B.V. All rights reserve
d.