Fig. 4

Ascl1b transcriptional regulation by opposing Hdac1 and Notch activities. (A) Blockade of Notch signalling by DAPT in hdac1^s436 mutants [condition (xi)] results in the recovery of ascl1b expression at 32 hpf and 48 hpf (arrowheads) (n=15/15 for both developmental stages combined). Arrowheads indicate the expression domain of ascl1b. (B) DAPT treatment of hdac1^s436 mutants [condition (xi)] does not affect the expression of nkx2.2 (n=7/7), foxa2 (n=8/8) and shh (n=6/6) (arrowheads) at 48 hpf. Arrowheads indicate the expression domain of the respective genes in the ventral midline of the embryo. Scale bar: 50 µm. (C) VPA treatment of embryos on the Notch signalling mutant mindbomb (mib) background [condition (i)] is associated with recovery of ascl1b expression (n=11/11). (D) Model of transcriptional regulation of ascl1b by Hdac1 and the Notch pathway. Solid arrows indicate direct positive regulation. Lines with an orthogonal bar represent inhibition. The inhibitory arrow with a question mark above it, from Hdac1 to Her, takes account of the possibility that another Her gene (or another transcription factor of unknown identity) that represses ascl1b is in turn repressed by Hdac1.