Biomedical subjects
Publications and source records attributed to Andrew Hudson.
Several chiral thiepines were efficiently constructed using sulfur diimidazole in combination with a variety of bislithiated carbon fragments. The sulfur atom in these thiepines is found to be unusually unreactive compared to diphenylsulfide.
How do transcription factors control the fates of cells that express them? One class of plant transcription factors has recently been shown to function by regulating the synthesis of cytokinin and gibberellin hormones--mobile molecules more usually associated with long-distance signalling.
Understanding evolutionary change requires phenotypic differences between organisms to be placed in a genetic context. However, there are few cases where it has been possible to define an appropriate genotypic space for a range of species. Here we address this problem by defining a genetically controlled space that captures variation in shape and size between closely related species of Antirrhinum. The axes of the space are based on an allometric model of leaves from an F2 of an interspecific cross between Antirrhinum majus and Antirrhinum charidemi. Three principal components were found to capture most of the genetic variation in shape and size, allowing a three-dimensional allometric space to be defined. The contribution of individual genetic loci was determined from QTL analysis, allowing each locus to be represented as a vector in the allometric space. Leaf shapes and sizes of 18 different Antirrhinum taxa, encompassing a broad range of leaf morphologies, could be accurately represented as clouds within the space. Most taxa overlapped with, or were near to, at least one other species in the space, so that together they defined a largely interconnected domain of viable forms. It is likely that the pattern of evolution within this domain reflects a combination of directional selection and evolutionary tradeoffs within a high dimensional space.
The genus Streptocarpus comprises species with diverse body plans. Caulescent species produce leaves from a conventional shoot apical meristem (SAM), whereas acaulescent species lack a conventional SAM and produce only a single leaf (the unifoliate form) or clusters of leaves from the base of more mature leaves (the rosulate form). These distinct morphologies reflect fundamental differences in the role of the SAM and the process of leaf specification. A subfamily of KNOTTED-like homeobox (KNOX) genes are known to be important in regulating meristem function and leaf development in model species with conventional morphologies. To test the involvement of KNOX genes in Streptocarpus evolution, two parologous KNOX genes (SSTM1 and SSTM2) were isolated from species with different growth forms. Their phylogenetic analysis suggested a gene duplication before the subgeneric split of Streptocarpus and resolved species relationships, supporting multiple evolutionary origins of the rosulate and unifoliate morphologies. In S. saxorum, a caulescent species with a conventional SAM, KNOX proteins were expressed in the SAM and transiently downregulated in incipient leaf primordia. The ability of acaulescent species to initiate leaves from existing leaves was found to correlate with SSTM1 expression and KNOX protein accumulation in leaves and to reflect genetic differences at two loci. Neither locus corresponded to SSTM1, suggesting that cis-acting differences in SSTM1 regulation were not responsible for evolution of the rosulate and unifoliate forms. However, the involvement of KNOX proteins in leaf formation in rosulate species suggests that they have played an indirect role in the development of morphological diversity in Streptocarpus.
The leaves of higher plants develop distinct cell types along their adaxial-abaxial (dorsal-ventral) axes. Interaction between leaf primordium cells with adaxial and abaxial identities is necessary for lateral growth of the developing leaf blade. We show that the growth and asymmetry of leaves in Antirrhinum majus involves the related YABBY transcription factors GRAMINIFOLIA (GRAM) and PROLONGATA (PROL). GRAM is expressed in abaxial margins of organ primordia where it promotes lateral growth and abaxial cell fate. GRAM, however, is not needed for abaxial fate in the absence of adaxial cell specification, suggesting that it promotes abaxial fate by excluding adaxial identity. Although GRAM expression is abaxially restricted, it functions redundantly with its abaxially expressed paralogue, PROL, and with the ubiquitously expressed PHANTASTICA gene to promote adaxial identity via intercellular signalling. This non cell-autonomous behaviour is consistent with the ability of GRAM in only the abaxial most cell layer to direct normal development of more adaxial cells. The contrasting roles of GRAM in promoting and inhibiting adaxial identity might serve to reinforce and maintain the distinction between adaxial and abaxial domains in the growing leaf primordium.
The title compound is made by two routes. One route features the separate introduction of two sulfur atoms and a double Pummerer reaction while the other route contains a direct introduction of both sulfur atoms using disulfur diimidazole.
The CYCLOIDEA (CYC) and DICHOTOMA (DICH) genes encode related TCP transcription factors that control floral asymmetry in Antirrhinum majus. Analysis of sequences from relatives of Antirrhinum suggested that CYC and DICH arose from a gene duplication in an ancestor of the tribe Antirrhineae and have subsequently evolved at similar rates. Coding regions outside the conserved functional TCP and R domains differed by numerous indels, suggesting rapid evolution and low constraint on amino acid sequence. An analysis of variability within the genus Antirrhinum revealed very similar CYC alleles in 17 representative species, consistent with most of the species having diverged within the last 1 myr. Whereas substitution mutations appear to have accumulated constantly, one Antirrhinum CYC allele provided evidence for sporadic and rapid accumulation of insertion mutations.
Despite the tremendous success of Arabidopsis thaliana, no single model can represent the vast range of form that is seen in the approximately 250,000 existing species of flowering plants (angiosperms). Here, we consider the history and future of an alternative angiosperm model--the snapdragon Antirrhinum majus. We ask what made Antirrhinum attractive to the earliest students of variation and inheritance, and how its use led to landmark advances in plant genetics and to our present understanding of plant development. Finally, we show how the wide diversity of Antirrhinum species, combined with classical and molecular genetics--the two traditional strengths of Antirrhinum--provide an opportunity for developmental, evolutionary and ecological approaches. These factors make A. majus an ideal comparative angiosperm.
To increase the utility of Antirrhinum for genetic and evolutionary studies, we constructed a molecular linkage map for an interspecific hybrid A. majus x A. molle. An F(2) population (n = 92) was genotyped at a minimum of 243 individual loci. Although distorted transmission ratios were observed at marker loci throughout the genome, a mapping strategy based on a fixed framework of codominant markers allowed the loci to be placed into eight robust linkage groups consistent with the haploid chromosome number of Antirrhinum. The mapped loci included 164 protein-coding genes and a similar number of unknown sequences mapped as AFLP, RFLP, ISTR, and ISSR markers. Inclusion of sequences from mutant loci allowed provisional alignment of classical and molecular linkage groups. The total map length was 613 cM with an average interval of 2.5 cM, but most of the loci were aggregated into clusters reducing the effective distance between markers. Potential causes of transmission ratio distortion and its effects on map construction were investigated. This first molecular linkage map for Antirrhinum should facilitate further mapping of mutations, major QTL, and other coding sequences in this model genus.
BACKGROUND: In syncytial blastoderm Drosophila embryos, actin caps assemble during telophase. As the cell cycle progresses through interphase, these small caps expand and fuse to form pseudocleavage furrows that are structurally related to the cleavage furrows that assemble during somatic cell division. The molecular mechanism driving cell cycle coordinated actin reorganization from the caps to the furrows is not understood. RESULTS: We show that Drosophila embryos contain a typical Arp2/3 complex and that components of this complex localize to the margins of the expanding caps, to mature pseudocleavage furrows, and to somatic cell cleavage furrows during the postcellularization embryonic divisions. A mutation that disrupts the arpc1 subunit of Arp2/3 leads to spindle fusions that are characteristic of pseudocleavage furrow disruption. By contrast, this mutation does not significantly affect nuclear positioning during interphase, which is dependent on actin cap function. In vivo analysis of actin reorganization demonstrates that the arpc1 mutation does not prevent assembly of small actin caps but blocks cap expansion and furrow assembly as the cell cycle progresses through interphase. The scrambled gene is also required for cap expansion and furrow assembly, and Scrambled is required for Arp2/3 localization to the cap margins. CONCLUSIONS: The Drosophila Arp2/3 complex and Scrambled protein are required for actin cap expansion and pseudocleavage furrow formation during the syncytial blastoderm divisions. We propose that Scrambled-dependent localization of Arp2/3 to the margins of the expanding caps triggers local actin polymerization that drives cap expansion and pseudocleavage furrow assembly.
BACKGROUND: Petal spurs-tubular outgrowths that collect nectar-are considered key innovations because of their ability to change pollinator specificity and so cause reproductive isolation and speciation. Spurs have arisen frequently and rapidly in many taxa. To test their potential origins, we isolated spontaneous dominant mutations at two loci, HIRZ and INA, that cause novel outgrowths from Antirrhinum petals, resembling the petal spurs of closely related genera. RESULTS: HIRZ and INA were isolated and shown to encode similar KNOX homeodomain proteins that are normally expressed only in apical meristems and are likely to act redundantly. Both dominant mutations were caused by transposon insertions in noncoding regions that caused ectopic expression of functional transcripts, either in petals or in all lateral organs with more pleiotropic effects. Formation of a spur-like outgrowth, which resembled an ectopic petal tube, was dependent both on KNOX gene expression and dorsiventral asymmetry of the flower. CONCLUSIONS: These mutations provide an example of how petal spurs might evolve rapidly due to changes in regulatory gene expression.
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