Search PubMed⌕ Search

Biomedical subjects

M Noll

Publications and source records attributed to M Noll.

At least 55 records · Page 3Linked to original sources
PubMed1993

The gene for PAX7, a member of the paired-box-containing genes, is localized on human chromosome arm 1p36.

The murine Pax-7 gene and the cognate human gene, formerly designated HuP1, are members of the multigene paired-box-containing class of developmental regulatory genes first identified in Drosophila. By analysis of somatic cell hybrids segregating human chromosomes, the gene encoding PAX7 was localized to human chromosome 1. Fluorescence in situ hybridization confirmed this assignment and allowed mapping of the gene to the terminal region of the short arm (1p36) of the chromosome. Additionally, these results confirm the extensive homology between human chromosome 1p and the distal segment of mouse chromosome 4, extending from bands C5 through E2.

Animals↗
PubMed1993

Evolution and role of Pax genes.

Pax genes encode a class of highly conserved transcription factors containing a paired-domain. These factors play important roles in Drosophila and vertebrate development, for example, in segmentation and neurogenesis. Their developmental roles are assessed in terms of their participation in conserved gene networks and mechanisms that establish positional information.

Animals↗
PubMed1993

Molecular genetics of aristaless, a prd-type homeo box gene involved in the morphogenesis of proximal and distal pattern elements in a subset of appendages in Drosophila.

Viable aristaless (al) mutations of Drosophila affect pattern elements at both ends of the proximodistal axis in a subset of adult appendages. The al gene has been cloned and identified by P-element-mediated germ-line transformation with a genomic DNA fragment, which rescues a lethal mutation of al as well as aspects of the adult al phenotype. The al gene contains a prd-type homeo domain and a Pro/Gln-rich domain and, hence, probably encodes a transcription factor. Its transcript distribution in third-instar imaginal discs closely corresponds to the anlagen of the tissues that later become visibly affected in adult al mutants. The striking similarity of a bimodal al expression in different imaginal discs indicates that al is under the control of a "prepattern," which is shared at least among antennal, leg, and wing discs. The al gene is also transcribed during embryogenesis. Apart from a function in the ontogeny of specific larval head and tail organs, its embryonic transcript pattern suggests a possible role in early imaginal disc development.

Amino Acid Sequence↗
PubMed1993

Complex regulation of early paired expression: initial activation by gap genes and pattern modulation by pair-rule genes.

The paired gene is one of approximately 30 zygotic segmentation genes responsible for establishing the segmented body plan of Drosophila melanogaster. To gain insight into the mechanism by which the paired gene is expressed in a complex temporal and spatial pattern, we have examined paired protein expression in wild-type and mutant embryos. In wild-type embryos, paired protein is expressed in several phases. Initial expression in broad domains evolves into a pair-rule pattern of eight stripes during cellularization. Subsequently, a segment-polarity-like pattern of fourteen stripes emerges. Later, at mid-embryogenesis, paired is expressed in specific regions of the head and in specific cells of the central nervous system. Analysis of the initial paired expression in the primary pair-rule mutants even-skipped, runt and hairy, and in all gap mutants suggests that the products of the gap genes hunchback, Krüppel, knirps and giant activate paired expression in stripes. With the exception of stripe 1, which is activated by even-skipped, and stripe 8, which depends upon runt, the primary pair-rule proteins are required for subsequent modulation rather than activation of the paired stripes. The factors activating paired expression in the pair-rule mode appear to interact with those activating it along the dorsoventral axis.

Animals↗
PubMed1993

Analysis of the gooseberry locus in Drosophila embryos: gooseberry determines the cuticular pattern and activates gooseberry neuro.

The segment-polarity class of segmentation genes in Drosophila are primarily involved in the specification of sub-segmental units. In addition, some of the segment-polarity genes have been shown to specify cell fates within the central nervous system. One of these loci, gooseberry, consists of two divergently transcribed genes, gooseberry and gooseberry neuro, which share a paired box as well as a paired-type homebox. Here, the expression patterns of the two gooseberry gene products are described in detail. The gooseberry protein appears in a characteristic segment-polarity pattern of stripes at gastrulation and persists until head involution. It is initially restricted to the ectodermal and neuroectodermal germ layer, but is later detected in mesodermal and neuronal cells as well. The gooseberry neuro protein first appears during germ band extension in cells of the central nervous system and also, much later, in epidermal stripes and in a small number of muscle cells. P-element-mediated transformation with the gooseberry gene has been used to demonstrate that gooseberry transactivates gooseberry neuro and is sufficient to rescue the gooseberry cuticular phenotype in the absence of gooseberry neuro.

Animals↗
PubMed1992

The paired box gene pox neuro: a determinant of poly-innervated sense organs in Drosophila.

This study describes the structure and function of pox neuro (poxn), a gene previously isolated by virtue of a conserved domain, the paired box, which it shares with the segmentation genes paired and gooseberry. Its expression pattern has been analyzed, particularly during development of the PNS. We propose that poxn is a "neuroblast identity" gene acting in both the PNS and the CNS on the basis of the following evidence. Its expression is restricted to four neuronal precursors in each hemisegment: two neuronal stem cells (neuroblasts) in the CNS, and two sensory mother cells (SMCs) in the PNS. The SMCs that express poxn produce the poly-innervated external sense organs of the larva. In poxn- embryos, poly-innervated sense organs are transformed into mono-innervated. Conversely, ectopic expression of poxn in embryos transformed with a heat-inducible poxn gene can switch mono-innervated to poly-innervated sense organs. Expression of poxn in the wing disc is restricted to the SMCs of the poly-innervated sense organs, suggesting that poxn also determines the lineage of poly-innervated adult sense organs.

Amino Acid Sequence↗
PubMed1990

Network of interactions among pair-rule genes regulating paired expression during primordial segmentation of Drosophila.

A model of the trans-regulation of the Drosophila pair-rule segmentation gene, paired (prd), has been derived from the observed alterations in the distribution of prd transcripts during early embryogenesis in single and double pair-rule mutants. Important aspects of the model include the following features and implications: (i) The regulation of prd is subject to a regulatory hierarchy among pair-rule genes. In particular, it shows that prd is at the bottom of this hierarchy, mediating the transition from pair-rule to segment-polarity genes. The transition of the early 'pair-rule' to the 'segment-polarity' pattern of prd expression is regulated by the secondary pair-rule genes opa and odd. The model predicts the distributions of pair-rule gene products regulating prd at late syncytial blastoderm, e.g., that of opa. (ii) The initial activation of prd is independent of pair-rule genes. (iii) The regulation of prd is combinatorial and hence probably cooperative. Combination of one pair-rule gene product with different pair-rule proteins may lead to opposite regulatory effects on prd. Furthermore, we discuss a two-step conversion of the initial analogue specification of position along the anteroposterior axis into a digital code specified by combinations of active segment-polarity and homeotic genes.

Animals↗
PubMed1989

Conservation of the paired domain in metazoans and its structure in three isolated human genes.

Sequences homologous to the paired domain of Drosophila melanogaster have been conserved in species as distantly related as nematodes, sea urchins, or man. In particular, paired domains of three human genes, HuP1, HuP2 and HuP48, have been isolated and sequenced. Together with four Drosophila paired domains, they fall into two separate paired domain classes named according to their Drosophila members, paired--gooseberry and P29 class. The P29 class includes the mouse Pax 1 and the human HuP48 gene which are nearly identical in their sequenced portions and hence might be true homologues. In addition to the paired domain, the two human genes HuP1 and HuP2 share the highly conserved octapeptide HSIAGILG with the two gooseberry genes of Drosophila. Possible functions of the paired domain are discussed in the light of a predicted helix-turn-helix structure in its carboxy-terminal portion.

Amino Acid Sequence↗
PubMed1989

Isolation of two tissue-specific Drosophila paired box genes, Pox meso and Pox neuro.

Two new paired domain genes of Drosophila, Pox meso and Pox neuro, are described. In contrast to the previously isolated paired domain genes, paired and gooseberry, which contain both a paired and a homeo-domain (PHox genes), Pox meso and Pox neuro possess no homeodomain. Evidence suggesting that the new genes encode tissue-specific transcriptional factors and belong to the same regulatory cascade as the other paired domain genes includes (i) tissue-specific expression of Pox meso in the somatic mesoderm and of Pox neuro in the central and peripheral nervous system, (ii) nuclear localization of their proteins, (iii) dependence on prd activity and (iv) presence of the paired domain in genes of known regulatory activity. While no mutant phenotypes of Pox meso and Pox neuro have yet been discovered, a murine gene with a paired domain closely homologous to that of Pox meso has recently been identified with the undulated mutant. Both Pox meso and undulated are expressed in tissues derived from the somatic mesoderm. The five known Drosophila paired domains fall into three classes: (i) the prd,gsb-class, (ii) the Pox meso, undulated-class and (iii) the Pox neuro-class which probably includes the paired domain of the murine gene Pax 2.

Amino Acid Sequence↗
PubMed1988

Molecular characterization of spalt, a homeotic gene required for head and tail development in the Drosophila embryo.

The isolation, identification and structure of the spalt gene is described. This novel homeotic gene of Drosophila is required for the establishment of the posterior-most head and the anterior-most tail segments of the embryo. It encodes a small mRNA of 0.8 kb which is under the control of over 15 kb of upstream sequences as indicated by the phenotype of transformed embryos. The putative spalt protein contains internal repeats and other interesting structural motifs but no homeo box. The spalt transcript accumulates motifs but no homeo box. The spalt transcript accumulates to high levels in the segmental anlagen affected in mutant embryos but is also found in regions of the embryo where no functional requirement has been demonstrated.

Journal Article↗
PubMed1988

The role of localization of bicoid RNA in organizing the anterior pattern of the Drosophila embryo.

The organization of the anterior pattern in the Drosophila embryo is mediated by the maternal effect gene bicoid. bcd has been identified in an 8.7-kb genomic fragment by germ line transformants that completely rescue the mutant phenotype. The major transcript of 2.6 kb includes a homeobox with low homology to previously known homeoboxes, a PRD-repeat and a M-repeat. In situ hybridizations reveal that bcd is transcribed in the nurse cells. The mRNA is localized at the anterior tip of oocyte and early embryo until the cellular blastoderm stage. The localization of the transcript requires the function of the maternal effect genes exuperantia and swallow while transcript stability is reduced by functions depending on posterior group genes.

Alleles↗
PubMed1987

Does the timing of aneurysm surgery neglect the real problems of subarachnoid haemorrhage?

In 1984, in connection with the introduction of the calcium antagonist nimodipine, a new strategy for the treatment of subarachnoid haemorrhage (SAH) due to ruptured aneurysm was developed in our hospital. With no rigid regard to "timing" all patients undergo surgery as soon as possible. The only exception being those in Hunt and Hess grades IV and V without space-occupying intracranial haemorrhage and those bearing aneurysms of the vertebrobasilar circulation that are difficult of access. As soon as the risk of rebleeding has been eliminated surgically an active therapy against the possible consequences of SAH--cerebral vasospasm and simultaneous disturbances of autoregulation--is started. It consists in lowering the increased intracranial pressure, raising of mean arterial pressure and improving of rheological properties of the blood in order to prevent delayed build-up of neurological deficit due to ischaemia. It goes without saying that calcium antagonists are given from the very beginning of the patient's treatment even before operation. The advantages of this therapeutic concept are demonstrated by two series of non-selected consecutive patient material. The first series (A; n = 135) was treated between 1981 and 1984 before the change in treatment strategy, the second (B; n = 183) from 1984 to 1986 after that change. The overall mortality in series A was 27%, that in series B 20%. Operative mortality could be reduced from 22% to 16% in patients having undergone early operation and from 6% to 2% in patients with late surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Structure of two genes at the gooseberry locus related to the paired gene and their spatial expression during Drosophila embryogenesis.

The gooseberry (gsb) locus contains two closely linked genes, BSH9 and BSH4, which are structurally related to each other and to the paired (prd) gene. Sequence analysis of genomic DNA and cDNA shows that BSH9 and BSH4 can encode proteins of 427 and 452 amino acids, respectively. The structural homology between these two putative proteins and the prd protein consists essentially of two domains forming most of the amino-terminal halves of the proteins: the prd domain of 128 amino acids and a prd-type homeo domain of 60 amino acids, which is extended by 18 amino acids at its amino-terminal end. The temporal profiles of BSH9 and BSH4 transcripts, as characterized by Northern analysis, show a peak shortly after the peak of prd transcripts. The spatial distributions of BSH9 and BSH4 transcripts have been analyzed by in situ hybridization to whole-mount and sectioned embryos. BSH9 transcripts appear in the posterior ventrolateral part of each primordial segment throughout the embryo, including head and tail segments. Transcripts are initially restricted to the ectoderm, in which they arise as two spatially shifted and temporally delayed waves exhibiting double-segment periodicity and anteroposterior polarity. During germ-band extension, BSH9 is induced in the mesoderm in register with the ectoderm and neurectoderm and in the tail segments A9-A11. In contrast, BSH4 transcripts appear with a single-segment repeat, first, in the neurectoderm during germ-band extension and, later, in single neurons during neuronal differentiation. BSH9, BSH4, and prd are activated in cells that are in register along the anteroposterior axis of the embryo in the posterior parts of primordial segments comprising the posterior compartments of engrailed expression.

Age Factors↗
PubMed1986

Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila.

Extending our search for homologous domains of the Drosophila paired gene, two closely linked genes at the gooseberry locus have been isolated. Both genes are expressed with a single segment periodicity but with different spatial and temporal expression patterns. While the transcripts of one gene appear earlier and are equally distributed between ectoderm and mesoderm, those of the second gene accumulate preferentially in neuroblasts. The similarity of these expression patterns to the 14-band pattern of the paired gene suggests a functional relationship. Such a functional link may be reflected in the two structurally homologous domains shared with the paired gene: a new type of homeo box extended by 18 amino acids at the 5' end, and a new domain, the paired box, consisting of a sequence of 128-135 amino acids. Thus, together with the PRD repeat, the paired gene contains at least three different domains, each defining a gene set thought to be important for development.

Animals↗
PubMed1986

Structure of the segmentation gene paired and the Drosophila PRD gene set as part of a gene network.

The sequence of paired, a pair-rule gene required for segmentation in Drosophila, is presented. A search for genes with domains homologous to the paired gene was initiated and three homologues from a set of 12 were characterized with respect to temporal or spatial expression and sequence homologies. All four are transcribed in early development, one in the oocyte and during cleavage stages in the form of a gradient. In addition to the prd-specific his-pro repeat, some of the 12 genes contain M-repeats and two new types of homeo boxes not detectable by hybridization with the two known classes of homeo boxes. The observed linking of gene sets through combinations of homologies coding for protein domains is consistent with a general network concept of gene action.

Amino Acid Sequence↗