Tcf-Lef genes

In the nucleus, in the absence of the Wnt signal,TCF acts as a repressor of Wnt/Wg target genes (Brannon 1997, Bienz 1998 . Riese 1997; also in C. elegans Lin 1998). TCF can form a complex with Groucho (Cavallo 1998). The repressing effect of Groucho is mediated by interactions with Histone Deacetylases (HDAC, Chen 1999). b-catenin can convert TCF into a transcriptional activator of the same genes that are repressed by TCF alone (reviewed in Nusse, 1999). Two other key players in this complex are Legless (Bcl9) and Pygopus (Kramps 2002, Thompson 2002, Parker 2002).

The gene pop-1 in C. elegans is a target of the mom2/5 (Wnt/Fz) pathway, but has a phenotype opposite of those genes (Lin, 1995). TCFs can repress target genes when Wnt/Wg signaling is absent. TCFs can bind to Groucho proteins to mediate this repression.

Reviewed in Roose, 1999

 Human Gene

(Genecards)

 Mouse Genes

 Mutant Phenotype
 TCF1

HUGO name TCF7

 Mouse Tcf1 (official name Tcf7)
Thymocyte Differentiation
Verbeek S, et al.
additional neural tubes
defects in the formation of the placenta and
in the development of limb buds
in double mutant with Lef-1 KO Galceran 1999
Mammary tumors, accelerated by loss of Min/APC Roose 1999
Hindgut defects and transformation of the gastro-intestinal tract in TCF1, 4 double KO (Gregorieff et al, 2004)
TCF3

HUGO name TCF7L1

 Mouse Tcf3

Expanded and often duplicated axial mesoderm structures, including nodes and notochords (Merrill, 2004)

Headless gene (hdl) in Zebrafish, Kim 2000

essential in head formation

TCF4

HUGO name TCF7L2

 Mouse Tcf4

Official name Tcf7l2

Associated with type II diabetes in humans Grant 2006
Absence of epithelial stem cells in small intestine
Korinek et al, 1998
Hindgut defects and transformation of the gastro-intestinal tract in TCF1, 4 double KO (Gregorieff et al, 2004)

LEF1

HUGO name LEF1

(There is no TCF2 gene; LEF1 substitutes for TCF2)

 Mouse Lef1
Several organs affected, epithelial-mesenchymal interactions
van Genderen et al.
additional neural tube
defects in the formation of the placenta and
in the development of limb buds
in double mutant with TCF-1 KO Galceran 1999
Defects in pro-B cell proliferation and survival (Reya, 2000)
reduced cell death and vascular regression failure (Lobov 2005) (also in LRP5 and wnt7B mutants)
Inactivating mutations in human sebaceous tumors (Takeda, 2006)
 Chicken Lef-1 AER formation
 Xenopus Lef-1
(GenBank AF063831)
 
Pangolin/DTcf
(in The Interactive Fly)
 Pangolin/DTcf in Flybase  segment polarity
pop-1
 pop-1
C. elegans
mesoderm becomes endoderm
 son-1  C. elegans  antagonizes pop-1, behaves as postive regulator Wnt signal Jiang LI, et al.1999

Figure from Clevers H, et al.

TCF Lef structures