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Biomedical subjects

W J Gehring

Publications and source records attributed to W J Gehring.

At least 55 records · Page 3Linked to original sources
PubMed1997

Conservation of Pax-6 in a lower chordate, the ascidian Phallusia mammillata.

The Pax-6 genes of vertebrates and invertebrates encode transcription factors with both a paired domain and a homeodomain. They are expressed in the developing eye and in the central nervous system. Loss-of-function mutations in mammals and in flies result in a reduction or absence of eyes and targeted expression of the Drosophila and the mouse Pax-6 genes induces ectopic eye structures in Drosophila. These findings lead to the proposal that the morphogenesis of the different types of eyes is controlled by a Pax-6-dependent genetic pathway and that the various eye types are of monophyletic origin. We have isolated a Pax-6 homologous gene from the ascidian Phallusia mammillata, because ascidians occupy an important position in early chordate evolution. Furthermore, the Phallusia larva has a simple photosensitive ocellus. Phallusia Pax-6 shares extensive sequence identity and conserved genomic organization with the known Pax-6 genes of vertebrates and invertebrates. Expression of Phallusia Pax-6 is first detected at late gastrula stages in distinct regions of the developing neural plate. At the tailbud stage, it is expressed in the spinal cord and the brain vesicle, where the sensory organs (ocellus and otolith) form, suggesting an important function in their development. Ectopic expression of the ascidian Pax-6 gene in Drosophila leads to the induction of supernumerary eyes indicating a highly conserved gene regulatory function for Pax-6 genes.

Amino Acid Sequence↗
PubMed1996

Intron of the mouse Hoxa-7 gene contains conserved homeodomain binding sites that can function as an enhancer element in Drosophila.

The 5' flanking sequences and the intron of the mouse Hoxa-7 gene were searched for regulatory elements that can function in Drosophila. Only the intron is able to activate a lacZ fusion gene in various tissues of Drosophila embryos. This enhancer function requires a cluster of three homeodomain binding sites (HB1-element) that are also found in the introns of other Hox genes as well as in a putative autoregulatory element of Ultrabithorax (Ubx), the Drosophila homolog of Hoxa-7. If a single binding site in the autoregulatory element of fushi tarazu (ftz) is replaced by the HB1-element of Hoxa-7, the expression pattern is altered and newly controlled by the homeotic gene caudal (cad). These data suggest that HB1 is a potential target for different homeodomain proteins of both vertebrates and invertebrates.

Animals↗
PubMed1996

Isolation of a Pax-6 homolog from the ribbonworm Lineus sanguineus.

The Pax-6 genes of vertebrates and Drosophila encode transcription factors with highly conserved paired- and homeodomains. They are expressed in the nervous system and the developing eyes. Loss-of-function mutations in mammals and flies lead to a reduction or absence of the eyes. By ectopic expression of Pax-6 in Drosophila ectopic eyes can be induced, indicating a determinative role in eye morphogenesis. We have isolated a Pax-6 homolog of the ribbonworm Lineus sanguineus. This gene shares extensive sequence identity and several conserved splice sites with the mammalian and Drosophila genes. During head regeneration the L. sanguineus Pax-6 homolog is expressed in the central nervous system, in the cerebral organ, and in the eye region. These findings support the hypothesis that Pax-6 was present in primitive metazoa before the evolutionary separation of vertebrates and arthropods and suggest a fundamental role in eye and central nervous system development.

Amino Acid Sequence↗
PubMed1996

RNA binding and translational suppression by bicoid.

The anterior determinant bicoid (bcd) of Drosophila is a homeodomain protein. It forms an anterior-to-posterior gradient in the embryo and activates, in a concentration-dependent manner, several zygotic segmentation genes during blastoderm formation. Its posterior counterpart, the homeodomain transcription factor caudal (cad), forms a concentration gradient in the opposite direction, emanating from evenly distributed messenger RNA in the egg. In embryos lacking bcd activity as a result of mutation, the cad gradient fails to form and cad becomes evenly distributed throughout the embryo. This suggests that bcd may act in the region-specific control of cad mRNA translation. Here we report that bcd binds through its homeodomain to cad mRNA in vitro, and exerts translational control through a bcd-binding region of cad mRNA.

Animals↗
PubMed1996

The master control gene for morphogenesis and evolution of the eye.

The human Aniridia, the murine Small eye, and the eyeless mutations of Drosophila affect homologous (Pax-6) genes that contain both a paired- and a homeobox. By ectopic expression of these genes, functional eyes can be induced on the legs, wings, and antennae of the fly, indicating that eyeless (Pax-6) is the master control gene for eye morphogenesis. The finding of Pax-6 from flatworms to humans suggests that eyeless is a universal master control gene and that the various types of eyes in the various animal phyla may have evolved from a single prototype.

Animals↗
PubMed1996

Event-related brain potentials and error-related processing: an analysis of incorrect responses to go and no-go stimuli.

Recent research has suggested that there is a component of the event-related brain potential, the error-related negativity (ERN), that is associated with error detection and remedial actions such as error inhibition, immediate error correction, or error compensation. The present experiment used a go/no-go task to define more precisely the functional significance of this component. In this task, an ERN was observed for incorrect responses on go trials (errors of choice) and for responses on no-go trials (errors of action). Because errors of action cannot be corrected immediately by executing another response, these results indicate that the process manifested by the ERN is not dependent on immediate error correction. Other aspects of the data converge in suggesting that the ERN process is more closely related to error detection and that the connections between detection and remedial actions may depend on the task situation.

Adult↗
PubMed1996

The Drosophila Serum Response Factor gene is required for the formation of intervein tissue of the wing and is allelic to blistered.

The adult Drosophila wing is formed by an epithelial sheet, which differentiates into two non-neural tissues, vein or intervein. A large number of genes, many of them encoding components of an EGF-receptor signaling pathway, have previously been shown to be required for differentiation of vein tissue. Much less is known about the molecular control of intervein differentiation. Here we report that the Drosophila homolog of the mammalian Serum Response Factor gene (DSRF), which encodes a MADS-box containing transcriptional regulator, is expressed in the future intervein tissue of wing imaginal discs. In adult flies carrying only one functional copy of the DSRF gene, additional vein tissue develops in the wing, indicating that DSRF is required to spatially restrict the formation of veins. In mitotic clones lacking DSRF, intervein tissue fails to differentiate and becomes vein-like in appearance. Genetic and molecular evidence demonstrates that DSRF is encoded by the blistered locus, which produces ectopic veins and blistered wings when mutant. Our results show that DSRF plays a dual role during wing differentiation. It acts in a dosage-dependent [correction of dosage-dependant] manner to suppress the formation of wing veins and is required cell-autonomously to promote the development of intervein cells. We propose that DSRF acts at a key step between regulatory genes that define the early positional values in the developing wing disc and the subsequent localized expression of intervein-specific structural genes.

Alleles↗
PubMed1995

Heat shock protein synthesis and thermotolerance in Cataglyphis, an ant from the Sahara desert.

The ant Cataglyphis lives in the Sahara desert and is one of the most thermotolerant land animals known. It forages at body temperatures above 50 degrees C, and the critical thermal maxima are at 53.6 +/- 0.8 degrees C for Cataglyphis bombycina and 55.1 +/- 1.1 degrees C for Cataglyphis bicolor. The synthesis and accumulation of heat shock proteins (HSPs) were analyzed in Cataglyphis and compared to Formica, an ant living in more moderate climates, and to two Drosophila species. In Cataglyphis, protein synthesis continues at temperatures up to 45 degrees C as compared to 39 degrees C for Formica and Drosophila. The two Drosophila species, Drosophila melanogaster and Drosophila ambigua, differ with respect to their maximal induction of HSP synthesis and accumulation by 3-4 degrees C. In contrast, the two ant species accumulate HSPs prior to their exposure to heat, and in Cataglyphis the temperature of maximal HSP induction by de novo protein synthesis is only 2 degrees C higher than in Formica. These findings are interpreted as preadaption of the ants prior to exposure to high temperatures.

Acclimatization↗
PubMed1995

Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila.

The Drosophila gene eyeless (ey) encodes a transcription factor with both a paired domain and a homeodomain. It is homologous to the mouse Small eye (Pax-6) gene and to the Aniridia gene in humans. These genes share extensive sequence identity, the position of three intron splice sites is conserved, and these genes are expressed similarly in the developing nervous system and in the eye during morphogenesis. Loss-of-function mutations in both the insect and in the mammalian genes have been shown to lead to a reduction or absence of eye structures, which suggests that ey functions in eye morphogenesis. By targeted expression of the ey complementary DNA in various imaginal disc primordia of Drosophila, ectopic eye structures were induced on the wings, the legs, and on the antennae. The ectopic eyes appeared morphologically normal and consisted of groups of fully differentiated ommatidia with a complete set of photoreceptor cells. These results support the proposition that ey is the master control gene for eye morphogenesis. Because homologous genes are present in vertebrates, ascidians, insects, cephalopods, and nemerteans, ey may function as a master control gene throughout the metazoa.

Animals↗
PubMed1995

Developmental defects in brain segmentation caused by mutations of the homeobox genes orthodenticle and empty spiracles in Drosophila.

We have studied the roles of the homeobox genes orthodenticle (otd) and empty spiracles (ems) in embryonic brain development of Drosophila. The embryonic brain is composed of three segmental neuromeres. The otd gene is expressed predominantly in the anterior neuromere; expression of ems is restricted to the two posterior neuromeres. Mutation of otd eliminates the first (protocerebral) brain neuromere. Mutation of ems eliminates the second (deutocerebral) and third (tritocerebral) neuromeres. otd is also necessary for development of the dorsal protocerebrum of the adult brain. We conclude that these homeobox genes are required for the development of specific brain segments in Drosophila, and that the regionalized expression of their homologs in vertebrate brains suggests an evolutionarily conserved program for brain development.

Animals↗
PubMed1995

New perspectives on eye evolution.

The highly complex eyes of vertebrates, insects and molluscs have long been considered to be of independent evolutionary origin. Recently, however, Pax-6, a highly conserved transcription factor, has been identified as a key regulator of eye development in both mammals and flies. Homologues of Pax-6 have also been identified in species from other phyla, including molluscs. The wide variety of eyes in the animal kingdom may, therefore, have evolved from a single ancestral photosensitive origin.

Animals↗
PubMed1994

Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans.

A Drosophila gene that contains both a paired box and a homeobox and has extensive sequence homology to the mouse Pax-6 (Small eye) gene was isolated and mapped to chromosome IV in a region close to the eyeless locus. Two spontaneous mutations, ey2 and eyR, contain transposable element insertions into the cloned gene and affect gene expression, particularly in the eye primordia. This indicates that the cloned gene encodes ey. The finding that ey of Drosophila, Small eye of the mouse, and human Aniridia are encoded by homologous genes suggests that eye morphogenesis is under similar genetic control in both vertebrates and insects, in spite of the large differences in eye morphology and mode of development.

Amino Acid Sequence↗
PubMed1994

Functional redundancy: the respective roles of the two sloppy paired genes in Drosophila segmentation.

The sloppy paired (slp) locus consists of two genes, slp1 and slp2, both of which encode proteins containing a forkhead domain (a DNA-binding motif). Previous work has shown that a severe segmentation phenotype is obtained only when both slp genes are deleted. Here we examine the functional redundancy of the locus in more detail. The phenotypes of embryos containing various combinations of functional slp genes suggest that for early slp function, until gastrulation, only slp1 is required. At later times, there is still a greater requirement for slp1, but in many respects the two slp genes are completely redundant. Both slp genes produce similar phenotypes when ubiquitously expressed via a heat shock promoter. We propose that the slp proteins are biochemically equivalent and that the greater requirement for slp1 in some functions can be explained in large part by its earlier expression.

Animals↗
PubMed1994

Nuclear magnetic resonance solution structure of the fushi tarazu homeodomain from Drosophila and comparison with the Antennapedia homeodomain.

The three-dimensional structure of a recombinant 70-residue polypeptide containing the complete fushi tarazu (ftz) homeodomain from Drosophila melanogaster has been determined by nuclear magnetic resonance (NMR) spectroscopy in solution. On the basis of 915 upper distance constraints derived from nuclear Overhauser effects and 178 dihedral angle constraints, a group of 20 conformers representing the solution structure of the ftz homeodomain was computed with the program DIANA and energy-minimized with the program OPAL. The average of the pairwise root-mean-square deviations of the individual NMR conformers relative to the mean coordinates is 0.50 A for the backbone atoms N, C alpha and C' of residues 8 to 53. The molecular architecture includes three helices comprising the residues 10 to 21, 28 to 38, and 42 to 52, a loop of residues 22 to 27 between the helices I and II, and a turn of residues 39 to 41 linking the helices II and III. Comparisons with the structure of the mutant Antennapedia homeodomain with Cys39 replaced by Ser, Antp (C39S), shows that the two proteins contain the same molecular fold for residues 8 to 53, whereas the more flexible fourth helix comprising residues 53 to 59 in the Antp (C39S) homeodomain has no counterpart in the ftz homeodomain. Considering that important intermolecular interactions in the DNA complexes with the Antp, engrailed and Mat alpha 2 homeodomains involve the fourth helix, it was rather unexpected that the stability of the complex of ftz with the BS2 operator site was found to be comparable to or even somewhat higher than that of the Antp complex with BS2. Another difference is that the Antp homeodomain is more stable with respect to thermal denaturation, with denaturation temperatures at pH 4.8 of 27 degrees C and 48 degrees C, respectively, for ftz and Antp.

Amino Acid Sequence↗
PubMed1994

The des(1-6)antennapedia homeodomain: comparison of the NMR solution structure and the DNA-binding affinity with the intact Antennapedia homeodomain.

The nuclear magnetic resonance (NMR) solution structure of an N-terminally truncated mutant Antennapedia homeodomain, des(1-6)Antp(C39S), has been determined from 935 nuclear Overhauser effect upper distance constraints and 148 dihedral angle constraints by using the programs DIANA and OPAL. Twenty conformers representing the solution structure of des(1-6)Antp(C39S) have an average root-mean-square distance relative to the mean coordinates of 0.56 A for the backbone atoms of residues 8-59. Comparison with the intact Antp(C39S) homeodomain shows that the two proteins have identical molecular architectures. The removal of the N-terminal residues 1-6, which are flexibly disordered in the intact homeodomain, causes only strictly localized structure variations and does not noticeably affect the adjoining helix I from residues 10-21. The DNA-binding constant of des(1-6)Antp(C39S) is approximately 10-fold reduced relative to the intact Antp(C39S) homeodomain, which can now be attributed to the absence of the previously reported contacts of the N-terminal polypeptide segment of the intact Antp(C39S) homeodomain with the minor groove of the DNA duplex.

Amino Acid Sequence↗
PubMed1994

Localized expression of sloppy paired protein maintains the polarity of Drosophila parasegments.

During germ-band extension in the Drosophila embryo, intercellular communication is required to maintain gene expression patterns initiated at cellular blastoderm. For example, the wingless (wg) single-cell-wide stripe in each parasegment (PS) is dependent on a signal from the adjacent, posterior cells, which express engrailed (eN). This signal is thought to be the hedgehog (hh) gene product, which antagonizes the activity of patched (ptc), a repressor of wg expression. Genetic evidence indicates that the hh signal is bidirectional, but wg transcription is only derepressed on the anterior side of the en/hh stripes. To explain the asymmetric response of the wg promoter to the hh signal, current models predict that each PS is divided into cells that are competent to express either wg or en, but not both. The sloppy paired (slp) locus contains two transcription units, both encoding proteins containing a forkhead domain, a DNA-binding motif. Removal of slp gene function causes embryos to exhibit a severe pair-rule/segment polarity phenotype. We show that the en stripes expand anteriorly in slp mutant embryos and that slp activity is an absolute requirement for maintenance of wg expression at the same time that wg transcription is dependent on hh. The slp proteins are expressed in broad stripes just anterior of the en-positive cells, overlapping the narrow wg stripes. We propose that by virtue of their ability to activate wg and repress en expression, the distribution of the slp proteins define the wg-competent and en-competent groups. Consistent with this hypothesis, ubiquitous expression of slp protein throughout the PS abolishes en expression and, in ptc mutant embryos, results in a near ubiquitous distribution of wg transcripts. In addition to demonstrating the role of slp in maintaining segment polarity, our results suggest that slp works in, or parallel with, the ptc/hh signal transduction pathway to regulate wg transcription.

Animals↗