Complementary expression pattern of Zfhx1 genes Sip1 and δEF1 in the mouse embryo and their genetic interaction revealed by compound mutants

Abstract

In mouse embryos, the Zfhx1 transcription factor genes, Sip1 and ␦EF1, are expressed in complementary domains in many tissues. Their possible synergism in embryogenesis was investigated by comparing the phenotype of Sip1؊/؊;␦EF1؊/؊ double homozygotes with single homozygous embryos. Unexpectedly, in Sip1؊/؊ embryos ␦EF1 was ectopically activated, suggesting a negative regulation of ␦EF1 expression by Sip1. Sip1؊/؊;␦EF1؊/؊ embryos were similar to Sip1؊/؊ embryos in short somite production and developmental arrest around E8.5, but showed more severe defects in dorsal neural tube morphogenesis accompanied by a larger reduction of Sox2 expression, ascribable to the loss of the ectopic ␦EF1 expression. Sip1؉/؊;␦EF1؊/؊ embryos develop various morphological defects after E10 that were absent in ␦EF1؊/؊ embryos even in tissues without significant overlap of Sip1 and ␦EF1 expression, and arrested during mid gestation earlier than ␦EF1؊/؊ embryos. These findings indicate that complex synergistic interactions occur between Zfhx1 transcription factor genes during mouse embryogenesis. Developmental Dynamics 235: 1941-1952, 2006.

The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-cadherin Transcriptional Repressors ZEB1 and ZEB2

“…Expression of the miR-200 family was found to be enriched in epithelial tissues (21,22) and negatively correlated with ZEB1 and ZEB2 expression during embryonic development (23). In addition, the ZEB family has been implicated in EMT, tumorigenesis, and metastasis (24 -27).…”

Differentiation of the Drosophila serotonergic lineage depends on the regulation of Zfh-1 by Notch and Eagle

“…The C. elegans homolog of Zfh-1, ZAG-1, is expressed both in muscle and the nervous system and is required for differentiation and axonal guidance of both motor neurons and interneurons (Clark and Chiu, 2003;Wacker et al, 2003). Vertebrates have two Zfh-1 homologs that are widely expressed and have been shown to affect development in a variety of tissues such as thymus, skeletal, muscle, lens and specific neural crest cells (Bassez et al, 2004;Higashi et al, 1997;Maruhashi et al, 2005;Miyoshi et al, 2006;Muraoka et al, 2000;Postigo et al, 1999;Takagi et al, 1998;Van de Putte et al, 2003;Yoshimoto et al, 2005). The mouse homologs have been shown to bind Smads and can regulate BMP signaling (Postigo, 2003).…”

Expression of ZEB factors in oral squamous cell carcinoma.

“…In Drosophila, Zfh-1 represents the mammalian ZEB superfamily, and Drosophila Zfh2 represents ATBF1, Zfh4, ZFh5, subfamily (Miyoshi, Maruhashi et al 2006). In humans, the ZEB family contains two members, ZEB1 and ZEB2.…”

“…Figure 1 shows the domain structures of ZEB1 and ZEB2. Both ZEB1 and ZEB2 bind to an identical consensus DNA sequence (CACCT) and when they are bound to this consensus sequence, they typically act as transcriptional repressors (Miyoshi, Maruhashi et al 2006). This binding involves only the zinc fingers, and not the centrally located homeodomain (Furusawa, Moribe et al 1999).…”

“…Elevated ZEB2 levels have also been observed in several types of cancer including: breast, ovarian, gastrin, and oral squamous cell carcinoma (Rosivatz, Becker et al 2002) By binding to the E-cadherin promoter, ZEB2 represses its transcription (Miyoshi, Maruhashi et al 2006). In addition to suppressing cell adhesion, ZEB2 has also demonstrated a protective effect on bladder cancer cells from DNA damage induced apoptosis.…”