Mutated in colorectal cancer (Mcc), a candidate tumor suppressor, is dynamically expressed during mouse embryogenesis

Abstract

Mutated in Colorectal Cancer (MCC) encodes a multiple PSD‐95/Dlg/ZO‐1 (PDZ) domain‐containing protein implicated, as its name suggests, in the pathogenesis of human colon cancer. To date, however, what role, if any, MCC plays in normal tissue homeostasis and development remains unclear. In an effort to expand our understanding of MCC function and distribution, we examined the expression of the evolutionarily conserved mouse Mcc homolog between embryonic days (E) 6.5 and 12.5 using conventional whole‐mount in situ hybridization and two independent Mcc reporter alleles. Mcc is expressed in the posterior primitive streak during gastrulation and in diverse tissues of both mesodermal and endodermal origin. In addition, Mcc transcripts localize to the posterior neural tube and identify discrete neuronal subtypes and ganglia within the developing central nervous system. Genetically, however, Mcc is entirely dispensable, as mice homozygous for the MccGt(D062B07) gene trap allele, which generates a loss‐of‐function mutation, are viable and fertile, with no ostensible phenotype. Developmental Dynamics 240:2166–2174, 2011. © 2011 Wiley‐Liss, Inc.

The PDZ domain protein Mcc is a novel effector of non-canonical Wnt signaling during convergence and extension in zebrafish

“…We previously reported that Mcc null mice are viable and fertile (Young et al, 2011). This dramatic difference between the zebrafish knockdown and mouse loss-of-function phenotypes most likely originates from species-specific differences in early Mcc/mcc expression and/or in the unique cell movements that each organism deploys during gastrulation and formation of the body axis (Solnica-Krezel and Sepich, 2012).…”

“…1A; supplementary material Table S1). Although two isoforms of Mcc differing only at their extreme N-termini are generated by alternative promoter usage in human and mouse (Young et al, 2011), we were unable to identify an mcc transcript encoding the shorter isoform 2 after exhaustive 5′-RACE and EST database searches. Given the length of the zebrafish Mcc polypeptide, we have therefore provisionally designated it as the longer isoform 1 (supplementary material Table S1).…”

“…Lastly, we recently observed enriched MCC expression in a microarray screen comparing the differentiation of human embryonic stem cells in response to combinations of TGFβ-related growth factors (Teo et al, 2012). High levels of MCC coincided with the expression of cardinal gastrulation marker genes and, in the mouse embryo, Mcc is specifically expressed in the primitive streak -the site of epithelial-to-mesenchymal transformation in the pluripotent epiblast, where nascent mesoderm and definitive endoderm emerge during gastrulation (Young et al, 2011). Collectively, these findings suggest that MCC activity is intimately linked to the actin cytoskeleton and the regulation of cell shape and morphogenesis.…”

Mutated in colorectal cancer (MCC) is a novel oncogene in B lymphocytes

“…In addition, an SNP of the MCC gene (rs11283943) is significantly associated with increased risk of breast cancer [28]. Although an inactivating MCC mutation in mice alone failed to induce any evident CRCs, the homozygous mice displayed a slightly higher proliferation rate of the epithelial crypt cells [29,30]. Interestingly, an unbiased genetic screening of a mouse model of CRC implicated MCC mutation as a key event in colorectal carcinogenesis [18].…”

“…It has been shown that during development, MCC is expressed in diverse tissues derived from all three embryonic germ layers, including the developing gut and central nervous system [29]. In adults, MCC is expressed in the surface epithelium of the colon and villi of the small intestines as well as other tissues, including the cerebellar cortex, kidney, pancreas, and liver [31,37].…”