Angiomotin is a novel component of cadherin-11/ β-catenin/p120 complex and is critical for cadherin-11-mediated cell migration.

The embryonic pattern of global DNA methylation is first established in the inner cell mass (ICM) of the mouse blastocyst The methyl donor S-adenosylmethionine (SAM) is produced in most cells through the f olate cycle, but only a few cell types generate SAM from betaine (N, N,N-trimethylglycine) via betaine-homocysteine meth-yltransferase (BHMT), which is expressed in the mouse ICM. Here, mean ICM cell numbers decreased from 18-19 in controls to 11-13 when the f olate cycle was inhibited by the antifolate methotrexate and to 12-14 when BHMT expression was knocked down by antisense morpholinos. Inhibiting both pathways, however, much more severely affected ICM development (7-8 cells). Total SAM levels in mouse blastocysts decreased significantly only when both pathways were inhibited (from 3.1 to 1.6 pmol/100 blastocysts). DNA methylation, detected as 5-methylcytosine (5-MeC) immunofluorescence in isolated ICMs, was minimally affected by inhibition of either pathway alone but decreased by at least 45-55% when both BHMT and the folate cycle were inhibited simultaneously. Effects on cell numbers and 5-MeC levels in the ICM were completely rescued by methionine (immediate SAM precursor) or SAM. Both the f olate cycle and betaine/BHMT appear to contribute to a methyl pool required for normal ICM development and establishing initial embryonic DNA methylation. [ABSTRACT FROM AUTHOR]