Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia.
The elaborate spatial and temporal patterns of gene expression generated during vertebrate embryogenesis are mediated by a large array of transcription factors. Homeodomain proteins constitute a major class of transcription factors responsible for this refined program of embryonic gene expression [reviewed by Duboule (Duboule 1994)]. Members of this family are characterised by the possession of a tripartite helical homeodomain, which recognises the core binding site TAAT and mediates the primary component of homeodomain protein functional specificity [reviewed by Gehring (Gehring et al., 1994)]. Further specificity in homeodomain-DNA interactions is generated by the ninth residue in the third helix of the homeodomain, which binds the two bases immediately 3′ to this core (Schier and Gehring, 1992; Treisman et al., 1989; Wilson et al., 1993). However, the broad classes of specificity generated by recognition of the TAAT core and its flanking sequences does little to define specific DNA sequences recognised by individual homeodomain proteins (Desplan et 5189 Development 128, 5189-5199 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV14511