The mouse homeobox gene Not is required for caudal notochord development and affected by the truncate mutation

Abstract

The floating head (flh) gene in zebrafish encodes a homeodomain protein, which is essential for notochord formation along the entire body axis. flh orthologs, termed Not genes, have been isolated from chick and Xenopus, but no mammalian ortholog has yet been identified. Truncate (tc) is an autosomal recessive mutation in mouse that specifically disrupts the development of the caudal notochord. Here, we demonstrate that truncate arose by a mutation in the mouse Not gene. The truncate allele (Not , and Not tc/tc embryos is very similar but slightly more severe in Not eGFP/eGFP than in Not tc/tc embryos. This confirms allelism of truncate and Not, and indicates that tc is not a complete null allele. Not expression is abolished in Foxa2 and T mutant embryos, suggesting that Not acts downstream of both genes during notochord development. 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.

PCR-based identification of short deletion/insertions and single nucleotide substitutions in genotyping of splotch (Pax3sp) and truncate (Nototc) mouse mutants

“…Decrease in the number of homozygotes born versus the number expected was already reported in similar studies. Moreover, detection of the homozygotes with normal tail morphology was in accordance with the previously reported variable severity of the Noto tc phenotype [9,11]. Theoretical possibility that the homozygote would be recognized as a heterozygote did not occur, as the mice without a tail were never recognized as heterozygotes.…”

“…Two representative mouse lines were tested: splotch, Pax3 mutant (Pax3 sp ) which carried a short deletion/insertion of 6 bp (Pax3:c.456-7T_-2AdelinsCGTGTG) [8] and truncate, Noto mutant (Noto tc ), which carried a SNS (Noto:c.503T>G) [9]. Splotch homozygous embryos often die due to heart and neural tube defects.…”

Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions

“…10,11 This complex functions as a general transcription regulation complex and is ubiquitously expressed. Abdelkhalek et al 12 showed that in mouse embryos loss of the ortholog Not results in abnormal notochord formation in and caudal to the posterior trunk.…”

Three types of cilia including a novel 9+4 axoneme on the notochordal plate of the rabbit embryo

“…The primary embryonic organizer, Spemann's organizer in the amphibian embryo, Hensen's node in rabbit and mouse, and the embryonic shield in the teleost fish embryo, from which the dorsal forerunner cells and hence Kupffer's vesicle (KV) are derived, thus sets the stage for the development of the PNC/GRP/KV or its equivalent in other vertebrates, which func-tionally may turn out to be primarily involved in LR axis development. Experimental manipulation of the organizer thus affects all three body axes, while defects in PNC/GRP/KV cause laterality defects without affecting the main body axes (Herrmann and Kispert, 1994;Nonaka et al, 1998;Krebs et al, 2003;Przemeck et al, 2003;Abdelkhalek et al, 2004).…”