Expression and splice variant analysis of the zebrafish tcf4 transcription factor

Abstract

Wnt signalling has been implicated in antero-posterior patterning of the vertebrate embryonic body axis and in a number of other developmental processes. One of the downstream effectors of Wnt signalling is the beta-catenin protein which complexes with members of the Lef/tcf transcription factor family. In the zebrafish, specification of the head has been shown to be dependent on the Tcf3 protein which acts as a repressor of the posteriorizing activity of Wnt (Nature 407 (2000) 913). Here, we report the cloning and expression pattern of the zebrafish tcf4 gene. In embryos, we find that the tcf4 gene is highly regulated at the level of RNA splicing such that the variant proteins that are produced contain or lack domains proposed to be essential in repression or activation of transcription. Expression of tcf4 mRNA is first detected in a graded fashion in the anterior brain and subsequently becomes restricted to the dorsal diencephalon and anterior midbrain. There is also transient expression in the anterior rhombomeres of the hindbrain and in the developing gut.

The β-catenin/VegT-regulated early zygotic geneXnr5is a direct target of SOX3 regulation

“…There are four known LEF/TCFs in vertebrates -TCF1, LEF1, TCF3 and TCF4 -three of which (TCF1, TCF3 and TCF4) are present as maternal RNAs in Xenopus. LEF1 (Hovanes et al, 2000), TCF1 and TCF4 (Duval et al, 2000;Young et al, 2002) transcripts occur in alternatively spliced variants that produce polypeptide variants. The activity of LEF/TCF appears to be determined by promoter context and associations with accessory factors.…”

Wnt signalling: variety at the core

“…The equivalent exon is always included in invertebrate TCFs and in vertebrate TCF-3 and TCF-4. However, this exon is differently spliced to the preceding exon and to the subsequent exon in TCF-4 to give rise to isoforms with or without LVPQ and SxxSS motifs (Duval et al, 2000;Pukrop et al, 2001;Young et al, 2002). These motifs appear always to be present in vertebrate TCF-3 (e.g.…”

nil per osencodes a conserved RNA recognition motif protein required for morphogenesis and cytodifferentiation of digestive organs in zebrafish

“…For example, some gene products required for epithelial morphogenesis or organ homeostasis are known to occur in multiple splice isoforms. Examples include fibronectin (Huerta et al, 2001;Inoue et al, 2001), epimorphin (Hirai, 2001;Lehnert et al, 2001) and TCF4 (Cho and Dressler, 1998;Young et al, 2002). Given that the Npo-related protein in yeast functions in splicing, it is plausible that, in metazoans, Npo could function by modulating isoform expression of developmentally important targets.…”