Biomedical subjects
Publications and source records attributed to A Hudson.
Three gene families have been identified which interact to polarize plant lateral organs. The results suggest that organ polarity is initially determined by a signal from the shoot tip which specifies adaxial organ identity and results in repression of abaxial identity, thereby aligning the polarity of organs with the stem.
The formation of many complex structures is controlled by a special class of transcription factors encoded by selector genes. It is shown that SCALLOPED, the DNA binding component of the selector protein complex for the Drosophila wing field, binds to and directly regulates the cis-regulatory elements of many individual target genes within the genetic regulatory network controlling wing development. Furthermore, combinations of binding sites for SCALLOPED and transcriptional effectors of signaling pathways are necessary and sufficient to specify wing-specific responses to different signaling pathways. The obligate integration of selector and signaling protein inputs on cis-regulatory DNA may be a general mechanism by which selector proteins control extensive genetic regulatory networks during development.
In angiosperms, individual lateral organs and whole flowers may develop asymmetrically along their dorsoventral axes. Dorsoventral asymmetry of Antirrhinum leaves requires activity of the Phantastica gene and other factors acting redundantly with it. We describe the effects of a mutation in the Handlebars gene, identified as an enhancer of the phantastica mutant phenotype. Genetic analysis suggests that Handlebars functions redundantly with Phantastica to promote dorsal fate in lateral organs and to maintain activity of stem cells within shoot apical meristems. Handlebars appears dispensable in vegetative development but is needed for asymmetry of petals along the dorsoventral axis of the flower as a whole. This suggests that common mechanisms may control dorsoventral asymmetry in lateral organ primordia and in floral meristems.
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The Drosophila Vestigial protein has been shown to play an essential role in the regulation of cell proliferation and differentiation within the developing wing imaginal disc. Cell-specific expression of vg is controlled by two separate transcriptional enhancers. The boundary enhancer controls expression in cells near the dorsoventral (DV) boundary and is regulated by the Notch signal transduction pathway, while the quadrant enhancer responds to the Decapentaplegic and Wingless morphogen gradients emanating from cells near the anteroposterior (AP) and DV boundaries, respectively. MAD-dependent activation of the vestigial quadrant enhancer results in broad expression throughout the wing pouch but is excluded from cells near the DV boundary. This has previously been thought to be due to direct repression by a signal from the DV boundary; however, we show that this exclusion of quadrant enhancer-dependent expression from the DV boundary is due to the absence of an additional essential activator in those cells. The Drosophila POU domain transcriptional regulator, Drifter, is expressed in all cells within the wing pouch expressing a vgQ-lacZ transgene and is also excluded from the DV boundary. Viable drifter hypomorphic mutations cause defects in cell proliferation and wing vein patterning correlated with decreased quadrant enhancer-dependent expression. Drifter misexpression at the DV boundary using the GAL4/UAS system causes ectopic outgrowths at the distal wing tip due to induction of aberrant Vestigial expression, while a dominant-negative Drifter isoform represses expression of vgQ-lacZ and causes severe notching of the adult wing. In addition, we have identified an essential evolutionarily conserved sequence element bound by the Drifter protein with high affinity and located adjacent to the MAD binding site within the quadrant enhancer. Our results demonstrate that Drifter functions along with MAD as a direct activator of Vestigial expression in the wing pouch.
P elements containing a 7 kb DNA fragment from the middle of the Drosophila bithorax complex insert preferentially into the bithorax complex or into the adjacent chromosome regions. This 'homing' property is similar to that reported for the engrailed promoter (Hama, C., Ali, Z. and Kornberg, T. B. (1990) Genes Dev. 4, 1079-1093). The 7 kb fragment does not contain any known promoter, but it acts as a boundary element separating adjacent segmental domains. An enhancer-trap P element was constructed with the homing fragment and the selectable marker flanked by FRT sites. P insertions can be trimmed down by Flp-mediated recombination to just the lacZ reporter, so that the (beta)-galactosidase pattern is not influenced by sequences inside the P element. Twenty insertions into the bithorax complex express (beta)-galactosidase in segmentally limited patterns, reflecting the segmental domains of the bithorax complex where the elements reside. The mapping of segmental domains has now been revised, with enlargement of the abx/bx, bxd/pbx, and the iab-3 domains. The FRT sites in the P elements permit recombination between pairs of elements on opposite chromosomes, to generate duplications or deletions of the DNA between the two insertion sites. Using this technique, the length of the Ultrabithorax transcription unit was varied from 37 to 138 kb, but there was surprisingly little effect on Ultrabithorax function.
The YABBY gene family was identified recently by homology to CRABS CLAW, a gene involved in carpel and nectary development in Arabidopsis. Several of the transcription factors encoded by the YABBY genes appear to have conserved roles in specifying abaxial cell fate in leaves, floral organs and ovules.
The regulation of members of the knotted1-like homeobox (knox) gene family is required for the normal initiation and development of lateral organs. The maize rough sheath2 (rs2) gene, which encodes a Myb-domain protein, is expressed in lateral organ primordia and their initials. Mutations in the rs2 gene permit ectopic expression of knox genes in leaf and floral primordia, causing a variety of developmental defects. Ectopic KNOX protein accumulation in rs2 mutants occurs in a subset of the normal rs2-expressing cells. This variegated accumulation of KNOX proteins in rs2 mutants suggests that rs2 represses knox expression through epigenetic means.
Adult survivors of childhood sexual abuse comprise a high percentage of the patients seen in gastrointestinal and genitourinary clinics and are commonly found among the patient population treated by WOC nurses. The physical and emotional consequences of sexual abuse may permeate the survivor's life, but rise to the forefront only with the additional stress of an ostomy or urinary diversion. Two case studies are described involving women the authors encountered in their practices.
Formation of leaves and floral organs involves down-regulation of meristem-specific homeobox genes, and de novo expression of genes for organ identity, growth and patterning. Genes required for all these aspects of organ formation have been identified. The challenge now is to establish how they interact to direct organogenesis.
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A small number of major regulatory (selector) genes have been identified in animals that control the development of particular organs or complex structures. In Drosophila, the vestigial gene is required for wing formation and is able to induce wing-like outgrowths on other structures. However, the molecular function of the nuclear Vestigial protein, which bears no informative similarities to other proteins, was unknown. Here, we show that Vestigial requires the function of the Scalloped protein, a member of the TEA family of transcriptional regulators, to directly activate the expression of genes involved in wing morphogenesis. Genetic and molecular analyses reveal that Vestigial regulates wing identity by forming a complex with the Scalloped protein that binds sequence specifically to essential sites in wing-specific enhancers. These enhancers also require the direct inputs of signaling pathways, and the response of an enhancer can be switched to another pathway through changes in signal-transducer binding sites. Combinatorial regulation by selector proteins and signal transducers is likely to be a general feature of the tissue-specific control of gene expression during organogenesis.
The organs of a higher plant show two fundamental axes of asymmetry: proximodistal and dorsoventral. Dorsoventrality in leaves, bracts, and petal lobes of Antirrhinum majus requires activity of the PHANTASTICA (PHAN) gene. Conditional mutants revealed that PHAN is also required for earlier elaboration of the proximodistal axis. PHAN was isolated and shown to encode a MYB transcription factor homolog. PHAN mRNA is first detected in organ initials before primordium initiation. The structure and expression pattern of PHAN, together with its requirement in two key features of organ development, are consistent with a role in specifying lateral organ identity as distinct from that of the stem or meristem. PHAN also appears to maintain meristem activity in a non-cell-autonomous manner.
Arthropods and vertebrates are constructed of many serially homologous structures whose individual patterns are regulated by Hox genes. The Hox-regulated target genes and developmental pathways that determine the morphological differences between any homologous structures are not known. The differentiation of the Drosophila haltere from the wing through the action of the Ultrabithorax (Ubx) gene is a classic example of Hox regulation of serial homology, although no Ubx-regulated genes in the haltere have been identified previously. Here, we show that Ubx represses the expression of the Wingless (Wg) signaling protein and a subset of Wg- and Decapentaplegic-activated genes such as spalt-related, vestigial, Serum Response Factor, and achaete-scute, whose products regulate morphological features that differ between the wing and haltere. In addition, we found that some genes in the same developmental pathway are independently regulated by Ubx. Our results suggest that Ubx, and Hox genes in general, independently and selectively regulate genes that act at many levels of regulatory hierarchies to shape the differential development of serially homologous structures.
Morphological studies of early events in leaf development have been hindered by the lack of stereotypic patterns of cell division and markers for cell identity. However, molecular genetic analysis, particularly in maize, has begun to suggest the mechanisms which partition meristematic cells into a leaf primordium, define regional identities within the primordium and direct localised growth which leads to outgrowth and flattening of the leaf. Therefore, the leaf may provide a model for pattern formation applicable to other parts of the plant.
Synaptojanin 1 is an inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Goal of this study was to provide new evidence for this hypothesis. We show that synaptojanin 1 is concentrated at clathrin-coated endocytic intermediates in nerve terminals. Furthermore, we report that synaptojanin-170, an alternatively spliced isoform of synaptojanin 1, binds Eps15, a clathrin coat-associated protein. Binding is mediated by the COOH-terminal region of synaptojanin-170 which we show here to be poorly conserved from rat to humans, but to contain in both species three asparagine-proline-phenylalanine (NPF) repeats. This motif has been found to be the core of the binding site for the EH domains of Eps15. Together with previous data, our results suggest that synaptojanin 1 can be recruited to clathrin-coated pits via a multiplicity of interactions.
Genetic and molecular analysis in Arabidopsis has identified components of a putative cell signalling pathway that appears to regulate the balance between stem cell proliferation and fate specification in meristems.
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