Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins

Mutations in the fushi tarazu (ftz) locus of Drosophila result in embryos with half the usual number of body segments. The sequences of the wild-type gene, a temperature-sensitive allele and a dominant mutant allele are presented. A portion of the conserved protein domain present in ftz and several homoeotic genes resembles the DNA-binding region of prokaryotic DNA-binding proteins, and is also similar to products of the yeast mating-type locus.     

Maternal control of Drosophila segmentation gene expression

Several genes have been identified that are involved in establishing the segmented body pattern during development of the fruit-fly Drosophila melanogaster. These fall into several classes on the basis of the kind of alteration to the wild-type segmentation pattern observed in mutant embryos. For example, mutations of the pair-rule class, such as fushi tarazu (ftz), cause the deletion of pattern elements with a two-segment periodicity; those of the gap class, such as knirps, cause the deletion of contiguous groups of segments. The availability of antibodies against the ftz protein has allowed its spatial pattern of expression to be studied during the development of wild-type and mutant embryos. The aim of the latter kind of experiment is to investigate possible interactions between these important genes. We have recently reported that knirps mutations cause a striking alteration to the pattern of transverse stripes of ftz expression usually seen during embryogenesis. Knirps is a zygotically-expressed gene, but recently a class of maternally-active genes has been identified that causes similar defects in pattern formation. We have now investigated the pattern of ftz expression in mutants of this class and have found that while they do have features seen in knirps mutants, they also exhibit significant differences between the different mutations reflecting the distinct but overlapping domains of gene activity. These observations demonstrate that maternally-active segmentation genes regulate zygotic gene expression, and that some of their effects on ftz may be directed through the knirps gene.     

A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes

A gene mapping to the sex-determining region of the mouse Y chromosome is deleted in a line of XY female mice mutant for Tdy, and is expressed at a stage during male gonadal development consistent with its having a role in testis determination. This gene is a member of a new family of at least five mouse genes, related by an amino-acid motif showing homology to other known or putative DNA-binding domains.     

Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11

The gene lin-11 is required for the asymmetric division of a vulval precursor cell type in the nematode Caenorhabditis elegans. Putative lin-11 complementary DNAs were sequenced and found to encode a protein that contains both a homeodomain and two tandem copies of a novel cysteine-rich motif: C-X2-C-X17-19-H-X2-C-X2-C-X2-C-X7-11-(C)-X8-C. Two tandem copies of this motif are also present amino-terminal to the homeodomains in the proteins encoded by the genes mec-3, which is required for C. elegans touch neuron differentiation, and isl-1, which encodes a rat insulin I gene enhancer-binding protein. The arrangement of cysteine residues in this motif, referred to as LIM (for lin-11 isl-1 mec-3), suggests that this region is a metal-binding domain. The presence in these three proteins of both a potential metal-binding domain and a homeodomain distinguishes them from previously characterized proteins.     

Regulation of segment polarity genes in the Drosophila blastoderm by fushi tarazu and even skipped

During the late cellular blastoderm stage of Drosophila embryo-genesis the segmentation genes engrailed, en, and wingless, wg, become expressed in two series of 14 stripes which will subsequently coincide with the anterior and posterior limits of each parasegment. Previous studies have shown that the establishment of the pattern of en stripes depends upon the activity of the homoeobox-containing pair-rule genes fushi tarazu, ftz and even skipped, eve. Here we show that these two genes also control the spatial expression of wg. Whereas ftz and eve behave as activators of en we find that both genes are required to repress wg expression, so that wg becomes expressed only in the narrow stripes of cells which come to separate the ftz and eve bands at the end of the blastoderm stage. In contrast, we propose that the precise positioning of the en stripes depends upon signals generated in a combinatorial manner by the overlaps between the ftz or eve domains and those of other pair rule genes, specifically odd paired, opa and paired, prd.     

Borders of parasegments in Drosophila embryos are delimited by the fushi tarazu and even-skipped genes

One of the earliest molecular signs of segmentation in Drosophila embryos is the striped expression of some pair-rule genes during the blastoderm stage. Two of these genes, fushi-tarazu (ftz) and even-skipped (eve) are expressed during this stage in complementary patterns of seven stripes which develop and disappear in concert. Here, we map the cells expressing each of these two pair-rule genes with respect to the 14 stripes of cells expressing the engrailed gene. We find that both ftz and eve generate stripes which have sharp boundaries at the anterior margin, but fade away posteriorly. The anterior boundaries correspond cell by cell with the anterior boundaries of expression of the engrailed gene. We therefore suggest that a key function of early ftz and eve gene activity is the formation of a sharp stable boundary at the anterior margin of each stripe. These boundary lines, rather than the narrowing zonal stripes, would delimit the anterior boundaries of engrailed and other homoeotic genes and thereby subdivide the embryo into parasegments.     

Control of neuronal fate by the Drosophila segmentation gene even-skipped

The central nervous system (CNS) contains a remarkable diversity of cell types. The molecular basis for generating this neuronal diversity is poorly understood. Much is known, however, about the regulatory genes which control segmentation and segment identity during early Drosophila embryogenesis. Interestingly, most of the segmentation and homoeotic genes in Drosophila, as well as many of their vertebrate homologues, are expressed during the development of the nervous system (for example, ref. 3). Are these genes involved in specifying the identity of individual neurons during neurogenesis, just as they specify the identity of cells during segmentation? We previously described the CNS expression of the segmentation gene fushi tarazu (ftz) and showed that ftz CNS expression is involved in the determination of an identified neuron. Here we show that another segmentation gene, even-skipped (eve), is expressed in a different but overlapping subset of neurons. Temperature-sensitive inactivation of the eve protein during neurogenesis alters the fate of two of these neurons. Our results indicate that the nuclear protein products of the eve and ftz segmentation genes are components of the mechanism controlling cell fate during neuronal development.