Fig. 12.

Working model for the actions of HDAC1/2 in the regulation of nephrogenesis. HDAC1/2 perform sequential functions during NPC and epithelial differentiation. (A) In the NPCs, HDAC1/2 are recruited (possibly by Six2/Sall1) to Six2 enhancer where they serve a positive regulatory role. HDAC1/2 also interact with Osr1 in the maintenance of NPCs. (B) HDAC1/2 in the NPCs and/or nascent nephrons restrain Wnt protein activity in adjacent stroma via unknown mechanisms. (C) HDAC1/2 directly or indirectly regulate the RV transcriptional network (Pax8/Fgf8/Lhx1) upstream of the Notch/HNF1A/HNF4A pathway. The dotted line indicates that NPC-specific deletion of HDAC1/2 arrests nephrogenesis at the RV stage.