Disease relevance of ntl

• To test whether esiRNA could work in zebrafish, we utilized Escherichia coli RNaseIII to digest dsRNA of zebrafish no tail (ntl), a mesoderm determinant in zebrafish and found that esi-ntl could lead to developmental defects, however, the effective dose was so close to the toxic dose that esi-ntl often led to non-specific developmental defects [1].

High impact information on ntl

• This is in contrast to zebrafish embryos, in which flh interacts with ntl (zebrafish T) in a regulatory loop and is essential for development of the entire notochord, and suggests that different genetic control circuits act in different vertebrate species during notochord formation [2].
• In contrast, morpholino- mediated knockdown of Spr2 activity inhibits ntl expression and reduces the inductive effect of Fgfs on ntl [3].
• We find that ntl function is required to repress medial floor plate and promote notochord fate in cells of the wild-type notochord domain and that spt and ntl together are required non cell-autonomously for medial floor plate formation, suggesting that an inducing signal present in wild-type mesoderm is lacking in spt(-);ntl(-) embryos [4].
• Overexpression of mezzo mRNA can induce ectopic expression of casanova and sox17 and can also turn on the pan mesodermal marker gene ntl [5].
• Classical mutations at the mouse Brachyury (T) locus were discovered because they lead to shortened tails in heterozygous newborns. no tail (ntl) mutants in the zebrafish, as their name suggests, show a similar phenotype [6].

Biological context of ntl

• Expression analysis of the transcription factors no tail (ntl) and goosecoid (gsc) by in situ hybridization suggests that these malformations are caused by altered cell migration during gastrulation [7].
• We propose a model to explain the FGF-dependent regulation of ntl and ntk that accounts for the above phenotypes [8].
• The amplifiable region of ctl was confined to the transcribed region of ntl. ctl thus appeared to have been generated by reverse transcription of ntl mRNA, like a processed pseudogene. ctl was very polymorphic even in individual fish, but had no missense mutations [9].
• Here, we show the presence of an intronless ntl gene in zebrafish, which we designated cryptail (ctl). ctl could not be found in any zebrafish genomic resources examined and was only just cloned by a PCR-based approach that relied on its lack of introns and homology to ntl [9].
• Second, free, DNA double-stranded ends (DSEs) were formed at an AT dinucleotide repeat in ntl [10].

Anatomical context of ntl

• These results reveal a redundant function of oep and ntl in mesoderm formation [11].
• Our data suggest that both oep and ntl act in the blastoderm margin to specify mesendodermal cell fates [11].
• Use of gsc as a dorsal marker allowed us to demonstrate that ntl expression is initially activated at the dorsal side of the blastula [12].
• Since the ntl mutant lacks the tail and notochord but has an otherwise normal trunk, this demonstrates that trunk development is dependent upon an unidentified gene, or set of genes, referred to as no trunk (ntk) which is regulated by FGF [8].
• Expression of a fibroblast growth factor (eFGF) or a dominant negatively acting FGF receptor shows that ntl but not gata5 is regulated by FGF signalling, implying that this may be the relay signal leading to the spread of ntl expression [13].

Regulatory relationships of ntl

• In spt long-pec mutant embryos, transcripts were expressed in two cranial muscle elements and the tail muscle region, but not in pectoral fin muscles, while only trace amounts of myhz2 MHC mRNA were expressed in the remaining tail muscle region of 38 hpf and long-pec ntl mutant embryos [14].

Other interactions of ntl

• These signals also induce the mesoderm-expressed transcription factor no tail (ntl), whose initial expression coincides with gata5 in the cells closest to the blastoderm margin, then spreads to encompass the germ ring [13].
• Thus, wnt11 and ntl expression are induced and maintained independently in their initial phase of expression [15].
• DSEs in ntl and nog2 had common characteristics, which suggested that the AT repeats in these genes elicited DSEs by blocking progression of the replication [10].
• The zebrafish T-box transcription factors spadetail (spt) and the brachyury ortholog no tail (ntl) are together essential for posterior mesoderm formation [16].
• Morpholino phenocopies of sqt, oep, and ntl mutations [17].

Analytical, diagnostic and therapeutic context of ntl

• Exposure of animal cap cells to activinA induces Zf-T expression, as does transplantation into the germ ring [18].
• Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization analysis showed that si-ntl could largely and specifically reduce mRNA levels of the ntl gene [1].
• 1. We found that microinjection of double-stranded Zf-T RNA resulted in a high incidence of a phenotype similar to that of ntl [19].

References