Biomedical subjects

E A Wimmer

Publications and source records attributed to E A Wimmer.

8 recordsLinked to original sources

PubMed1997

Embryonic expression and characterization of a Ptx1 homolog in Drosophila.

We describe the molecular characterization of the paired-type homeobox gene D-Ptx1 of Drosophila, a close homolog of the mouse pituitary homeobox gene Ptx1 and the unc-30 gene of C. elegans, characterized by a lysine residue at position 9 of the third alpha-helix of the homeodomain. D-Ptx1 is expressed at various restricted locations throughout embryogenesis. Initial expression of D-Ptx1 in the posterior-most region of the blastoderm embryo is controlled by fork head activity in response to the activated Ras/Raf signaling pathway. During later stages of embryonic development. D-Ptx1 transcripts and protein accumulate in the posterior portion of the midgut, in the developing Malpighian tubules, in a subset of ventral somatic muscles, and in neural cells. Phenotypic analysis of gain-of-function and lack-of-function mutant embryos show that the D-Ptx1 gene is not involved in morphologically apparent differentiation processes. We conclude that D-Ptx1 is more likely to control physiological cell functions than pattern formation during Drosophila embryogenesis.

Amino Acid Sequence↗

PubMed1997

buttonhead does not contribute to a combinatorial code proposed for Drosophila head development.

The Drosophila gap-like segmentation genes orthodenticle, empty spiracles and buttonhead (btd) are expressed and required in overlapping domains in the head region of the blastoderm stage embryo. Their expression domains correspond to two or three segment anlagen that fail to develop in each mutant. It has been proposed that these overlapping expression domains mediate head metamerization and could generate a combinatorial code to specify segment identity. To test this model, we developed a system for targeted gene expression in the early embryo, based on region specific promoters and the flp-out system. Misexpression of btd in the anterior half of the blastoderm embryo directed by the hunchback proximal promoter rescues the btd mutant head phenotype to wild-type. This indicates that, while btd activity is required for the formation of specific head segments, its ectopic expression does not disturb head development. We conclude that the spatial limits of btd expression are not instructive for metamerization of the head region and that btd activity does not contribute to a combinatorial code for specification of segment identity.

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PubMed1996

buttonhead and D-Sp1: a novel Drosophila gene pair.

The Drosophila gene buttonhead (btd) is a gap-like head segmentation gene which encodes a triple zinc finger protein structurally and functionally related to the human transcription factor Spl. Here we report the pattern of btd expression during embryogenesis. btd is not only expressed and required in the blastoderm anlagen of the antennal, intercalary and mandibular segments as reported previously, but both expression and requirement extend into the anlage of the maxillary segment. From gastrulation onwards, btd is expressed in distinct spatial and temporal patterns, suggesting that btd might be required for a number of developmental processes beyond head segmentation. In fact, analysis of btd mutant embryos revealed that btd participates in the formation of the peripheral nervous system. However, no other morphologically apparent phenotype was observed. We identified a btd-related gene, termed D-Sp1, which is expressed in temporal and spatial patterns similar to btd during postblastodermal development. No localized expression domains of D-Sp1, which is located in the same X-chromosomal band as btd, were seen during the blastoderm stage. The results suggest that D-Sp1 and btd represent a novel gene pair with partially redundant functions after the blastoderm stage.

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PubMed1995

Trans- and cis-acting requirements for blastodermal expression of the head gap gene buttonhead.

The Drosophila gene buttonhead (btd) encodes a zinc-finger protein related to the human transcription factor Sp1. btd is expressed in the syncytial blastoderm embryo in a stripe covering the anlagen of the antennal, intercalary and mandibular head segments. btd has been characterized as a head gap gene, since these segments are deleted in btd mutant embryos. We report here that the cis-acting elements required for btd head stripe expression are contained in a 1 kb DNA fragment, located about 3 kb upstream of the promoter. The four maternal coordinate systems are necessary for correct btd head stripe expression, likely by acting through the 1 kb cis-acting control region. Expression of the btd head stripe depends on the anterior morphogen encoded by the gene bicoid (bcd). bcd-dependent activation also involves the activity of the morphogens of the posterior and dorsoventral systems, hunchback and dorsal, respectively, which act together to control the spatial limits of the expression domain. Finally, the terminal system takes part in the regulation of btd head stripe expression by enhancing activation at low levels of activity and repression at high levels of activity.

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PubMed1994

Redundant functions of the genes knirps and knirps-related for the establishment of anterior Drosophila head structures.

Developmental gene functions of Drosophila are typically characterized by a recognizable mutant phenotype. When molecular probes of such genes were used to isolate homologues, distinct spatially and temporally restricted expression patterns were observed in vertebrates as well. However, corresponding "gene knock-outs" often revealed subtle or no scorable phenotypes, a phenomenon attributed to redundant gene functions. We found that the evolutionarily related genes knirps (kni) and knirps-related (knrl) contribute to a similar phenomenon in Drosophila. The two closely situated genes show identical expression patterns in the developing embryo, including the posterior and anterior expression domains in the blastoderm. Here we show that the two biochemically equivalent gene products are both functional in the head anlage and that the lack of one gene activity can be overcome by the activity of the other. Whereas kni is also required for abdominal segmentation, knrl is nonfunctional in its posterior expression domain. Thus, the kni/knrl pair of genes provides a region-specific buffering system, rather than a case of global functional redundancy.

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PubMed1994

Identical transacting factor requirement for knirps and knirps-related Gene expression in the anterior but not in the posterior region of the Drosophila embryo.

The Drosophila genes knirps (kni) and knirps-related (knrl) are located within the 77E1,2 region on the left arm of the third chromosome. They encode nuclear hormone-like transcription factors containing almost identical Cys2/Cys2 DNA-binding zinc finger motifs which bind to the same target sequence. kni is a member of the gap class of segmentation genes, and its activity is required for the normal establishment of the abdomen. The function of knrl is still unknown; however, a possible gap gene function in the abdominal region of the embryo can be excluded. Both genes are initially expressed in three identical regions of the blastoderm embryo: in an anterior cap domain, in an anterior stripe and in a posterior broad band linked to the kni gap gene function. The transacting factor requirement for the expression of kni and knrl is identical for the two anterior domains but different, although similar, for the posterior domain of expression in the blastoderm. Both the anteroposterior morphogen bicoid and the dorsoventral morphogen dorsal are necessary but not sufficient for the activation of the two genes in the anterior cap domain, suggesting they act together to bring about its normal spatial limits.

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PubMed1993

A Drosophila homologue of human Sp1 is a head-specific segmentation gene.

Segmentation in Drosophila is based on a cascade of hierarchical gene interactions initiated by maternally deposited morphogens that define the spatially restricted domains of gap gene expression at blastoderm (reviewed in ref. 1). Although segmentation of the embryonic head is morphologically obscured, the repeated patterns of expression of the segment polarity genes reflect the formation of seven head segments; two of these depend on the segmentation and homeotic genes used in the trunk, whereas the others form as a result of the activity of the head-specific genes orthodenticle (otd), empty spiracles (ems) and buttonhead (btd). The genes ems and otd encode homeodomain proteins, suggesting that they may function as transcription factors. They are expressed in overlapping stripes in the early embryonic head of Drosophila, and their vertebrate homologues, otx and emx, are expressed in overlapping domains in the anterior central nervous system of the mouse embryo. We show here that btd is expressed in a stripe covering the head analgen of the segments affected in btd lack-of-function mutants and that btd encodes a zinc-finger-type transcription factor with sequence and functional similarity to the prototype mammalian transcription factor Sp1 (ref. 9). When expressed in the spatial pattern of btd, a transgene providing Sp1 activity can support development of the mandibular segment in the head of btd mutant embryos. A ubiquitous transcription factor from humans can therefore replace an essential component of the genetic circuitry required to specify the development of a particular head segment in the fly.

Amino Acid Sequence↗

PubMed1991

Early development of leg and wing primordia in the Drosophila embryo.

The development of the leg and wing primordia in the Drosophila embryo has been traced using molecular markers. Distal-less and disconnected gene expression provide molecular labels for the leg primordia throughout embryonic development, disconnected expression in the developing leg primordia depends on Distal-less activity. The leg primordia arise as discrete clusters of cells that occupy well defined positions in the embryonic ectoderm. At later stages of embryogenesis the primordia become morphologically recognizable and are intimately associated with the development of the Keilin's organs. The presumptive leg disc and the Keilin's organ appear to derive from a common primordium. Similarly the Abnormal leg pattern gene provides a molecular label for the wing and haltere primordia. The dorsal thoracic primordia appear to be of independent origin from the legs.

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