Multiple faces of FoxM1 transcription factor: lessons from transgenic mouse models

Abstract

FoxM1 transcription factor (previously called HFH-11B, Trident, FoxM1b, Win, and MPP2) is expressed in actively dividing cells and critical for cell cycle progression. FoxM1 expression is induced in a variety of tissues during embryogenesis, and Foxm1 (-/-) mice exhibit embryonic lethal phenotype due to multiple abnormalities in the liver, heart, lung and blood vessels. FoxM1 levels are dramatically decreased in adult tissues, but FoxM1 expression is re-activated during organ injury and numerous cancers. In this review, we discussed the role of FoxM1 in different cell lineages using recent data from transgenic mouse models with conditional "gain-of-function" and "loss-of-function" of FoxM1, as well as tissue samples from human patients. In addition, we provided experimental data showing additional sites of FoxM1 expression in the mouse embryo. Novel cell-autonomous roles of FoxM1 in embryonic development, organ injury and cancer formation in vivo were analyzed. Potential application of these findings for the diagnosis and treatment of human diseases were discussed.

Figure 1

FoxM1 expression in the mouse embryo. Paraffin sections were prepared from mouse wild type embryos harvested at E13.5 (G–I and R), E15.5 (A, B, D and J–P) or E18.5 (C, E, F and Q). Sections were used for immunohistochemistry with FoxM1 antibodies (brown) and counterstained with nuclear fast red (red nuclei). Nuclear FoxM1 staining was detected in hair follicles (A and C), follicles of vibrissae (B) and keratinocytes of basal layers (A–C). FoxM1 was also observed in developing kidney (D–F), cartilage (J–L), epithelial and mesenchymal cells of pancreas and stomach (G and I). FoxM1 expressing cells were detected in nasal cavity (M), tongue (N), tooth primordium (O), salivary glands (P), muscles (Q) and the Rathke's pouch (R). sk, skin; hf, hair follicle; fv, follicle of vibrissae; ki, kidney; gl, glomeruli; li, liver; pa, pancreas; st, stomach; ca, cartilage; di, diaphragm; nc, nasal cavity; to, tongue; tp, tooth primordium; sg, salivary gland; m, muscle; Rp, Rathke's pouch. Magnification: (D, G, J and M) x50; (C, F and L) x400; (A, E and N–P) x100; remaining parts, x200.

Figure 2

Diagram showing direct FoxM1 target genes in different cell lineages.