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Biomedical subjects

J L Bowman

Publications and source records attributed to J L Bowman.

At least 19 recordsLinked to original sources

Establishment of polarity in lateral organs of plants.

BACKGROUND: Asymmetric development of plant lateral organs initiates by partitioning of organ primordia into distinct domains along their adaxial/abaxial axis. A recent model proposes that a meristem-born signal, acting in a concentration-dependent manner, differentially activates PHABULOSA-like genes, which in turn suppress abaxial-promoting factors. As yet, no abaxial factors have been identified that when compromised give rise to adaxialized organs. RESULTS: Single mutants in either of the closely related genes KANADI1 (KAN1) or KANADI2 (KAN2) have little or no effect on plant morphology. However, in kan1 kan2 double mutant plants, there is a replacement of abaxial cell types by adaxial ones in most lateral organs. The alterations in polarity establishment are associated with expansion in the expression domain of the PHB-like genes and reduction in the expression of the previously described abaxial-promoting YABBY genes. Ectopic expression of either of the KANADI genes throughout leaf primordia results in dramatic transformation of adaxial cell types into abaxial ones, failure of lateral blade expansion, and vascular tissue formation. CONCLUSION: The phenotypes of KANADI loss- and gain-of-function alleles suggest that fine regulation of these genes is at the core of polarity establishment. As such, they are likely to be targets of the PHB-mediated meristem-born signaling that patterns lateral organ primordia. PHB-like genes and the abaxial-promoting KANADI and YABBY genes appear to be expressed throughout primordia anlagen before becoming confined to their corresponding domains as primordia arise. This suggests that the establishment of polarity in plant lateral organs occurs via mutual repression interactions between ab/ad factors after primordium emergence, consistent with the results of classical dissection experiments.

Amino Acid Sequence↗

Turning floral organs into leaves, leaves into floral organs.

The development of the floral organs is specified by the combinations of three classes of gene for organ identity in the 'ABC' model. Recently, molecular genetic studies have shown this model is applicable to grass plants as well as most eudicots. Transcription factor complexes of ABC and homologous proteins form the molecular basis of the ABC model.

Arabidopsis↗

Subversion of the T/B lineage decision in the thymus by lunatic fringe-mediated inhibition of Notch-1.

Notch-1 signaling is essential for lymphoid progenitors to undergo T cell commitment, but the mechanism has not been defined. Here we show that thymocytes ectopically expressing Lunatic Fringe, a modifier of Notch-1 signaling, induce lymphoid progenitors to develop into B cells in the thymus. This cell fate switch resulted from Lunatic Fringe-mediated inhibition of Notch-1 function, as revealed by experiments utilizing lymphoid progenitors in which Notch-1 activity was genetically manipulated. These data identify Lunatic Fringe as a potent regulator of Notch-1 during the T/B lineage decision and show that an important function of Notch-1 in T cell commitment is to suppress B cell development in the thymus.

Animals↗

The Arabidopsis nectary is an ABC-independent floral structure.

In contrast to the conservation of floral organ order in angiosperm flowers, nectary glands can be found in various floral and extrafloral positions. Since in Arabidopsis, the nectary develops only at the base of stamens, its specification was assayed with regard to the floral homeotic ABC selector genes. We show that the nectary can form independently of any floral organ identity gene but is restricted to the 'third whorl' domain in the flower. This domain is, in part, specified redundantly by LEAFY and UNUSUAL FLORAL ORGANS. Even though nectary glands arise from cells previously expressing the B class genes, their proper development requires the down-regulation of B class gene activity. While CRABS CLAW is essential for nectary gland formation, its ectopic expression is not sufficient to induce ectopic nectary formation. We show that in Arabidopsis multiple factors act to restrict the nectary to the flower, and surprisingly, some of these factors are LEAFY and UNUSUAL FLORAL ORGANS.

Antigens, Differentiation↗

SHATTERPROOF MADS-box genes control seed dispersal in Arabidopsis.

The fruit, which mediates the maturation and dispersal of seeds, is a complex structure unique to flowering plants. Seed dispersal in plants such as Arabidopsis occurs by a process called fruit dehiscence, or pod shatter. Few studies have focused on identifying genes that regulate this process, in spite of the agronomic value of controlling seed dispersal in crop plants such as canola. Here we show that the closely related SHATTERPROOF (SHP1) and SHATTERPROOF2 (SHP2) MADS-box genes are required for fruit dehiscence in Arabidopsis. Moreover, SHP1 and SHP2 are functionally redundant, as neither single mutant displays a novel phenotype. Our studies of shp1 shp2 fruit, and of plants constitutively expressing SHP1 and SHP2, show that these two genes control dehiscence zone differentiation and promote the lignification of adjacent cells. Our results indicate that further analysis of the molecular events underlying fruit dehiscence may allow genetic manipulation of pod shatter in crop plants.

Arabidopsis↗

Axial patterning in leaves and other lateral organs.

The establishment of abaxial-adaxial polarity in lateral organs involves factors intrinsic to the primordia and interactions with the apical meristem from which they are derived. Recent molecular genetic studies have identified some of the genes that promote either adaxial or abaxial cell fates, with many of the genes encoding spatially localized transcription factors.

Animals↗

Formation and maintenance of the shoot apical meristem.

Development in higher plants is characterized by the reiterative formation of lateral organs from the flanks of shoot apical meristems. Because organs are produced continuously throughout the life cycle, the shoot apical meristem must maintain a pluripotent stem cell population. These two tasks are accomplished within separate functional domains of the apical meristem. These functional domains develop gradually during embryogenesis. Subsequently, communication among cells within the shoot apical meristem and between the shoot apical meristem and the incipient lateral organs is needed to maintain the functional domains within the shoot apical meristem.

Meristem↗

The YABBY gene family and abaxial cell fate.

The establishment of abaxial-adaxial polarity in lateral organs involves factors intrinsic to the primordia and interactions with the apical meristem from which they are derived. Recently, a small plant-specific family of genes, the YABBY gene family, has been proposed to specify abaxial cell fate. Each asymmetric above-ground lateral organ expresses at least one member of the family in a polar manner, and loss- and gain-of-function studies indicate that they are sufficient to specify abaxial cell fate and that they act in both distinct and redundant manners.

Cell Differentiation↗

An algorithm for abdominal wall reconstruction.

Acquired abdominal wall defects result from trauma, previous surgery, infection, and tumor resection. The correction of complex defects is a challenge to both plastic and reconstructive and general surgeons. The anatomy of the abdominal wall, as well as considerations in patient assessment and surgical planning, are discussed. A simple classification of abdominal wall defects based on size, depth, and location is provided. Publications regarding the various abdominal reconstruction techniques are reviewed and summarized to familiarize the reader with the treatment options for each particular defect. Finally, an algorithm is presented to guide the surgeon in selecting the optimal reconstructive technique.

Abdominal Muscles↗

Endoscopically assisted "components separation" for closure of abdominal wall defects.

The repair of ventral hernia defects of the abdominal wall challenges both general and plastic surgeons. Ventral herniation is a postoperative complication in 10 percent of abdominal surgeries; the repair of such defects has a recurrence rate as high as 50 percent. The "components separation" technique has successfully decreased the recurrence rates of ventral abdominal hernias. However, this technique has been associated with midline dehiscence and a prolonged postoperative stay at the authors' institutions. The purpose of this study was to determine whether endoscopically assisted components separation could minimize operative damage to the vasculature of the abdominal wall and decrease postoperative wound dehiscence. The study group consisted of seven patients who underwent endoscopically assisted components separation; the control group consisted of 30 patients who underwent open components separation. The two groups were similar regarding demographic data and defect size. The endoscopic group had a higher initial success rate than the open group (100 versus 77 percent). Recurrence rates were not significantly different between the two groups. However, the endoscopically assisted components separation patients had fewer postoperative and long-term complications. In the authors' experience, endoscopically assisted components separation has proved to be a safe and effective method for the repair of complicated and recurrent midline ventral hernias.

Abdominal Muscles↗

Mechanisms that control knox gene expression in the Arabidopsis shoot.

Knotted1-like homeobox (knox) genes are expressed in specific patterns within shoot meristems and play an important role in meristem maintenance. Misexpression of the knox genes, KNAT1 or KNAT2, in Arabidopsis produces a variety of phenotypes, including lobed leaves and ectopic stipules and meristems in the sinus, the region between lobes. We sought to determine the mechanisms that control knox gene expression in the shoot by examining recessive mutants that share phenotypic characteristics with 35S::KNAT1 plants. Double mutants of serrate (se) with either asymmetric1 (as1) or asymmetric2 (as2) showed lobed leaves, ectopic stipules in the sinuses and defects in the timely elongation of sepals, petals and stamens, similar to 35S::KNAT1 plants. Ectopic stipules and in rare cases, ectopic meristems, were detected in the sinuses on plants that were mutant for pickle and either as1 or as2. KNAT1 and KNAT2 were misexpressed in the leaves and flowers of single as1 and as2 mutants and in the sinuses of leaves of the different double mutants, but not in se or pickle single mutants. These results suggest that AS1 and AS2 promote leaf differentiation through repression of knox expression in leaves, and that SE and PKL globally restrict the competence to respond to genes that promote morphogenesis.

Arabidopsis↗

Distinct mechanisms promote polarity establishment in carpels of Arabidopsis.

Lateral organs of plants display asymmetry with abaxial identity being specified by members of the Arabidopsis YABBY gene family. Mutations in CRABS CLAW, the founding family member, display ectopic formation of adaxial carpel tissues only when the functions of other genes, such as GYMNOS or KANADI, are also compromised. Mutations in these genes alone do not result in loss of polar differentiation, and therefore, they act redundantly with CRABS CLAW to establish polarity. As GYMNOS encodes a uniformly expressed homolog of the chromatin-remodeling protein, Mi2, we argue that the unique genetic interactions do not reflect a molecular redundancy. Rather, CRABS CLAW regulates transcription spatially, whereas GYMNOS regulates downstream targets temporally to ensure proper differentiation of the carpels.

Arabidopsis↗

Molecular genetics of gynoecium development in Arabidopsis.

Carpels are the ovule-bearing structural units in angiosperms. In Arabidopsis, the specification of carpel identity is achieved by at least two separate pathways: a pathway mediated by the C class gene AG and an AG-independent pathway. Both pathways are negatively regulated by A class genes. Two genes, SPT and CRC, can promote differentiation of carpel tissue independently of AG and are thus components of the AG-independent pathway. CRC and SPT appear to act in a redundant manner to promote the differentiation of subsets of carpel tissues. The carpel primordium is subdivided into regional domains, both medial versus lateral and abaxial versus adaxial. Based on morphological and gene expression analyses, it appears likely that these domains define developmental compartments. The medial domain appears fated to differentiate into the marginal tissue types of the carpel (septum with transmitting tract and placenta with ovules), whereas the lateral domain gives rise to the ovary walls. The expression of ETT defines the abaxial domain, and this gene is involved in the abaxial-adaxial and, possibly, the apical-basal patterning of tissues in the carpel. Once regional domains have been established, the differentiation of tissue and cell types occurs. The MADS-box gene FUL and AGLI/5 are involved in the differentiation of specific tissue types in the valves and valve margins. Thus, the genes identified can be arranged in a functional hierarchy: specification of carpel identity, patterning of the carpel primordium and directing the differentiation of the specialized tissues of the carpel.

Arabidopsis↗

CRABS CLAW, a gene that regulates carpel and nectary development in Arabidopsis, encodes a novel protein with zinc finger and helix-loop-helix domains.

Studies of plants with mutations in the CRABS CLAW gene indicate that it is involved in suppressing early radial growth of the gynoecium and in promoting its later elongation. It is also required for the initiation of nectary development. To gain further insight, the gene was cloned by chromosome walking. CRABS CLAW encodes a putative transcription factor containing a zinc finger and a helix-loop-helix domain. The latter resembles the first two helices of the HMG box, known to bind DNA. At least five other genes of Arabidopsis carry the same combination of domains, and we have named them the yabby family. The new helix-loop-helix domain itself we call the yabby domain. Consistent with the mutant phenotype, CRABS CLAW expression is mostly limited to carpels and nectaries. It is expressed in gynoecial primordia from their inception, firstly in lateral sectors where it may inhibit radial growth, and later in the epidermis and in four internal strips. The internal expression may be sufficient to support longitudinal growth, as carpels are longer in a crabs claw promoter mutant where expression is now confined to these regions. The patterns of expression of CRABS CLAW in ectopic carpels of floral homeotic mutants suggest that it is negatively regulated by the A and B organ identity functions, but largely independent of C function. CRABS CLAW expression occurs in nectaries throughout their growth and maturation. It is also expressed in their presumptive anlagen so it may specify cells that will later develop as nectaries. Nectaries arise from the floral receptacle at normal positions in all A, B and C organ identity mutants examined, and CRABS CLAW is always expressed within them. Thus CRABS CLAW expression is regulated independently in carpels and nectaries.

Amino Acid Sequence↗

Members of the YABBY gene family specify abaxial cell fate in Arabidopsis.

Lateral organs produced by shoot apical and flower meristems exhibit a fundamental abaxial-adaxial asymmetry. We describe three members of the YABBY gene family, FILAMENTOUS FLOWER, YABBY2 and YABBY3, isolated on the basis of homology to CRABS CLAW. Each of these genes is expressed in a polar manner in all lateral organ primordia produced from the apical and flower meristems. The expression of these genes is precisely correlated with abaxial cell fate in mutants in which abaxial cell fates are found ectopically, reduced or eliminated. Ectopic expression of either FILAMENTOUS FLOWER or YABBY3 is sufficient to specify the development of ectopic abaxial tissues in lateral organs. Conversely, loss of polar expression of these two genes results in a loss of polar differentiation of tissues in lateral organs. Taken together, these observations indicate that members of this gene family are responsible for the specification of abaxial cell fate in lateral organs of Arabidopsis. Furthermore, ectopic expression studies suggest that ubiquitous abaxial cell fate and maintenance of a functional apical meristem are incompatible.

Amino Acid Sequence↗

Relative bioavailability of itraconazole from an extemporaneously prepared suspension and from the marketed capsules.

The bioavailability of itraconazole from an extemporaneously prepared suspension was compared with its bioavailability from the commercially available capsules. Ten healthy volunteers were fed breakfast and were then randomly assigned to receive either 400 mg of itraconazole 40-mg/mL oral suspension or four 100-mg itraconazole capsules with 240 mL of water. They were not allowed to rest in a supine position for six hours, eat for four hours, or take any beverages for two hours post-dose. Blood samples were taken immediately after the subjects had eaten and at intervals up to 72 hours post-dose. Serum was separated and stored at -70 degrees C. Serum itraconazole and hydroxyitraconazole concentrations were measured by high-performance liquid chromatography. After 14 days, each subject was given the dosage form that he or she did not previously receive, and testing was repeated. Maximum concentration (Cmax) and time to reach maximum concentration (tmax) were determined, and the area under the serum concentration-versus-time curve from 0 to 72 hours (AUC0-72) was estimated. The suspension:capsule ratios of least-squares means for Cmax, tmax, and AUC0-72 for itraconazole were 0.15 (90% confidence interval [CI], 0.11-0.21), 0.95 (90% CI, 0.75-1.20), and 0.12 (9% CI, 0.06-0.23), respectively. The results for hydroxyitraconazole were similar: 0.19 (0.13-0.28), 0.95 (0.81-1.12), and 0.13 (0.07-0.23), respectively. The bioavailability of itraconazole from the extemporaneously prepared suspension is much lower than that from capsules.

Adult↗

Manipulation of flower structure in transgenic tobacco.

Genetic studies suggest that three homeotic functions, designated A, B, and C, act alone and together to specify the fate of floral organ primordia in distantly related dicotyledonous plant species. To test the genetic model, we have generated transgenic tobacco plants that ectopically express the AGAMOUS gene from Brassica napus, which is necessary for the C function. Flowers on the resulting plants showed homeotic transformations of sepals into carpels and petals into stamens. These phenotypes are consistent with predictions from the genetic model, show that expression of AGAMOUS is sufficient to provide ectopic C function, and demonstrate that the structure of flowers can be manipulated in a predictable manner by altering the expression of a single regulatory gene. Furthermore, the generation of the predicted transformations by ectopic expression of the Brassica gene in transgenic tobacco indicates that gene functions are interchangeable between phylogenetically distant species.

Amino Acid Sequence↗

Vectors for plant transformation and cosmid libraries.

A series of vectors has been constructed for the purpose of introducing cloned DNAs into plant genomes, using Agrobacterium tumefaciens-mediated transformation methods. One of these vectors, pCIT20, is a plasmid that contains a multiple cloning site (MCS), and a marker (Hph) that confers hygromycin resistance to plant cells. The others are all cosmid vectors which allow insertion of up to 46 kb of plant genomic DNA, and which also contain all of the necessary sequences for A. tumefaciens-mediated plant transformation. The cosmid vectors either contain a Hph marker (pCIT30), or a kanamycin-resistance marker (pCIT101-104). Three of the cosmid vectors (pCIT30, pCIT101, and pCIT103) carry bacteriophage T7 and SP6 promoters flanking the cloning Bg/II site, for synthesis of end-specific RNAs. The end-specific RNAs may be used as probes when labeled with radioactive or biotinylated nucleotides, for example, in a chromosome-walking experiment. The other two cosmid vectors (pCIT102 and pCIT104) carry restriction sites flanking the insertion site (XhoI) for convenient release of the insert by restriction digests. These sites, in combination with sites internal to the insert, allow the generation of end fragments for subcloning or labeling probes. These vectors should be valuable for isolation and analysis of plant genes, using transformation, library screening, and chromosome-walking approaches.

Agrobacterium tumefaciens↗