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PubMed1989

Switch protein alters specificity of RNA polymerase containing a compartment-specific sigma factor.

During sporulation in Bacillus subtilis, expression of developmental genes spoIVCB and cotD is induced in the mother cell compartment of the sporangium at morphological stages IV and V, respectively. A 27-kilodalton RNA polymerase sigma factor called sigma K (or sigma 27) has been found that causes weak transcription of spoIVCB and strong transcription of cotD. A 14-kD protein was also discovered that changes the specificity of sigma K-containing RNA polymerase, greatly stimulating spoIVCB transcription and markedly repressing cotD transcription. Both sigma K and the 14-kD protein are products of genes known to be required for expression of specific genes in the mother cell. Thus, sigma K directs gene expression in the mother cell and it is proposed that inactivation or sequestering of the 14-kD protein switches the temporal pattern of gene expression during the transition from stages IV to V of development.

Amino Acid Sequence↗
PubMed2004

A WD40 repeat protein regulates fungal cell differentiation and can be replaced functionally by the mammalian homologue striatin.

Fruiting body development in fungi is a complex cellular differentiation process that is controlled by more than 100 developmental genes. Mutants of the filamentous fungus Sordaria macrospora showing defects in fruiting body formation are pertinent sources for the identification of components of this multicellular differentiation process. Here we show that the sterile mutant pro11 carries a defect in the pro11 gene encoding a multimodular WD40 repeat protein. Complementation analysis indicates that the wild-type gene or C-terminally truncated versions of the wild-type protein are able to restore the fertile phenotype in mutant pro11. PRO11 shows significant homology to several vertebrate WD40 proteins, such as striatin and zinedin, which seem to be involved in Ca2+-dependent signaling in cells of the central nervous system and are supposed to function as scaffolding proteins linking signaling and eukaryotic endocytosis. Cloning of a mouse cDNA encoding striatin allowed functional substitution of the wild-type protein with restoration of fertility in mutant pro11. Our data strongly suggest that an evolutionarily conserved cellular process controlling eukaryotic cell differentiation may regulate fruiting body formation.

Amino Acid Sequence↗
PubMed2006

Interactions between Streptomyces coelicolor and Bacillus subtilis: Role of surfactants in raising aerial structures.

Using mixed-species cultures, we have undertaken a study of interactions between two common spore-forming soil bacteria, Bacillus subtilis and Streptomyces coelicolor. Our experiments demonstrate that the development of aerial hyphae and spores by S. coelicolor is inhibited by surfactin, a lipopeptide surfactant produced by B. subtilis. Current models of aerial development by sporulating bacteria and fungi postulate a role for surfactants in reducing surface tension at air-liquid interfaces, thereby removing the major barrier to aerial growth. S. coelicolor produces SapB, an amphipathic peptide that is surface active and required for aerial growth on certain media. Loss of aerial hyphae in developmental mutants can be rescued by addition of purified SapB. While a surfactant from a fungus can substitute for SapB in a mutant that lacks aerial hyphae, not all surfactants have this effect. We show that surfactin is required for formation of aerial structures on the surface of B. subtilis colonies. However, in contrast to this positive role, our experiments reveal that surfactin acts antagonistically by arresting S. coelicolor aerial development and causing altered expression of developmental genes. Our observations support the idea that surfactants function specifically for a given organism regardless of their shared ability to reduce surface tension. Production of surfactants with antagonistic activity could provide a powerful competitive advantage during surface colonization and in competition for resources.

Bacillus subtilis↗
PubMed2006

Mutational analysis of the promoter recognized by Chlamydia and Escherichia coli sigma(28) RNA polymerase.

sigma(28) RNA polymerase is an alternative RNA polymerase that has been postulated to have a role in developmental gene regulation in Chlamydia. Although a consensus bacterial sigma(28) promoter sequence has been proposed, it is based on a relatively small number of defined promoters, and the promoter structure has not been systematically analyzed. To evaluate the sequence of the sigma(28)-dependent promoter, we performed a comprehensive mutational analysis of the Chlamydia trachomatis hctB promoter, testing the effect of point substitutions on promoter activity. We defined a -35 element recognized by chlamydial sigma(28) RNA polymerase that resembles the consensus -35 sequence. Within the -10 element, however, chlamydial sigma(28) RNA polymerase showed a striking preference for a CGA sequence at positions -12 to -10 rather than the longer consensus -10 sequence. We also observed a strong preference for this CGA sequence by Escherichia coli sigma(28) RNA polymerase, suggesting that this previously unrecognized motif is the critical component of the -10 promoter element recognized by sigma(28) RNA polymerase. Although the consensus spacer length is 11 nucleotides (nt), we found that sigma(28) RNA polymerase from both Chlamydia and E. coli transcribed a promoter with either an 11- or 12-nt spacer equally well. Altogether, we found very similar results for sigma(28) RNA polymerase from C. trachomatis and E. coli, suggesting that promoter recognition by this alternative RNA polymerase is well conserved among bacteria. The preferred sigma(28) promoter that we defined in the context of the hctB promoter is TAAAGwwy-n(11/12)-ryCGAwrn, where w is A or T, r is a purine, y is a pyrimidine, n is any nucleotide, and n(11/12) is a spacer of 11 or 12 nt.

Amino Acid Substitution↗
PubMed1981

Genetic characterization of aggregation-defective developmental mutants of Myxococcus xanthus.

The transposon Tn5 was used to map temperature-sensitive mutants of Myxococcus xanthus defective in aggregation (C. E. Morrison and D. R. Zusman, J. Bacteriol. 140:1036-1042, 1979). Seven of the eight mutants showing a similar terminal phenotype (rough) were found to be tightly linked. These mapped in a group of loci which we have designated aggR1, aggR2, aggR3, and aggR4. Temperature-sensitive mutants having a different terminal phenotype were not liked to aggR. A search through a group of nonconditional rough mutants indicated that a much lower proportion of these (1 of 35) mapped in aggR. Thus, aggR is probably only one of many sites which can lead to the rough phenotype when mutated. Localized mutagenesis was used to isolate nine additional aggR mutants. All mapped within aggR1, aggR2, or aggR3, and none was found outside this region. Thus, we have characterized a cluster of developmental genes which are needed for aggregation in M. xanthus. The localization of a Tn5 insert adjacent to this region makes possible further manipulation of these genes.

Chromosome Mapping↗
PubMed1994

Isolated fibrils rescue cohesion and development in the Dsp mutant of Myxococcus xanthus.

Extracellular fibrils are involved in cell cohesion and cell development in Myxococcus xanthus. One group of social motility mutants, Dsp, is unable to produce extracellular fibrils; these mutants also lose the abilities to cohere and to develop. Extracellular fibrils isolated from vegetative wild-type cells and added to Dsp cells fully restored the abilities of these cells to cohere and to undergo normal morphological development. The fibrils thus mimic the ability of intact, wild-type cells to carry out the same rescue. Optimal cohesion rescue by fibrils required calcium and magnesium ions, did not require protein synthesis, but was energy dependent, i.e., sodium azide and sodium cyanide blocked rescue. Cohesion rescue was also blocked by the diazo dye Congo red. Cohesion rescue is genus specific, i.e., isolated fibrils did not cause the cohesion of Pseudomonas aeruginosa, Bacillus subtilis, Proteus mirabilis, Escherichia coli, or the related myxobacterium Stigmatella aurantiaca. Developmental rescue of Dsp by isolated fibrils included aggregation, fruiting body formation, and myxospore morphogenesis. Developmental gene expression in the Dsp mutant was only partially rescued by the isolated fibrils.

Bacterial Adhesion↗
PubMed1995

Methionine inhibits developmental aggregation of Myxococcus xanthus by blocking the biosynthesis of S-adenosyl methionine.

Previous studies showed that high concentrations of methionine (> 1 mM) inhibited aggregation and fruiting body formation in Myxococcus xanthus (E. Rosenberg, D. Filer, D. Zafriti, and S. H. Kindler, J. Bacteriol. 115: 29-34, 1973, and J. M. Campos and D. R. Zusman, Proc. Natl. Acad. Sci. USA 72:518-522, 1975). However, the mechanism for the inhibition was unclear. In this study, we found that high levels of methionine inhibited the biosynthesis of S-adenosylmethionine (SAM) and that reduced intracellular levels of SAM are correlated with defective chemotactic movements and reduced developmental gene expression. In addition, we found that methionine analogs and high concentrations of amino acids which are known to affect SAM synthesis in other bacteria, such as threonine, lysine, and isoleucine, also caused reduced cellular levels of SAM and blocked fruiting body formation in M. xanthus. These results indicate that SAM is required for development of M. xanthus and the inhibitory effect of methionine on development results, at least in part, from its blocking of the biosynthesis of SAM.

Amino Acids↗
PubMed1997

Hierarchical autoinduction in Ralstonia solanacearum: control of acyl-homoserine lactone production by a novel autoregulatory system responsive to 3-hydroxypalmitic acid methyl ester.

Bacteria employ autoinduction systems to sense the onset of appropriate cell density for expression of developmental genes. In many gram-negative bacteria, autoinduction involves the production of and response to diffusible acylated-homoserine lactones (acyl-HSLs) and is mediated by members of the LuxR and LuxI families. Ralstonia (Pseudomonas) solanacearum, a phytopathogenic bacterium that appears to autoregulate its virulence genes, produces compounds that promote expression of several heterologous acyl-HSL-responsive reporter gene constructs. High-pressure liquid chromatography of highly concentrated ethyl acetate extracts revealed that culture supernatants of strain AW1 contained two compounds with retention times similar to N-hexanoyl- and N-octanoyl-HSL. To investigate the role of these acyl-HSLs in R. solanacearum virulence gene expression, transposon mutants that were deficient for inducing an acyl-HSL-responsive reporter in Agrobacterium tumefaciens were generated. Three loci involved in normal acyl-HSL production were identified, one of which was shown to contain the divergently transcribed solR and solI genes, the luxR and luxI homologs, respectively. A 4.1-kb fragment containing solR and solI enabled all of the mutants (regardless of the locus inactivated) and a naturally acyl-HSL-defective strain of R. solanacearum to produce acyl-HSLs. Inactivation of solI abolished production of all detectable acyl-HSLs but affected neither the expression of virulence genes in culture nor the ability to wilt tomato plants. AW1 has a functional autoinduction system, because (i) expression of solI required SolR and acyl-HSL and (ii) expression of a gene linked to solR and solI, designated aidA, was acyl-HSL dependent. Because AidA has no homologs in the protein databases, its discovery provided no clues as to the role of acyl-HSLs in R. solanacearum gene regulation. However, expression of solR and solI required the global LysR-type virulence regulator PhcA, and both solR and solI exhibited a cell density-associated pattern of expression similar to other PhcA-regulated genes. The acyl-HSL-dependent autoinduction system in R. solanacearum is part of a more complex autoregulatory hierarchy, since the transcriptional activity of PhcA is itself controlled by a novel autoregulatory system that responds to 3-hydroxypalmitic acid methyl ester.

4-Butyrolactone↗
PubMed1998

Coordination of initiation of nuclear division and initiation of cell division in Schizosaccharomyces pombe: genetic interactions of mutations.

sep1+ encodes a Schizosaccharomyces pombe homolog of the HNF-3/forkhead family of the tissue-specific and developmental gene regulators identified in higher eukaryotes. Its mutant allele sep1-1 causes a defect in cytokinesis and confers a mycelial morphology. Here we report on genetic interactions of sep1-1 with the M-phase initiation mutations wee1-, cdc2-1w, and cdc25-22. The double mutants sep1-1 wee1- and sep1-1 cdc2-1w form dikaryon cells at high frequency, which is due to nuclear division in the absence of cell division. The dikaryosis is reversible and suppressible by cdc25-22. We propose that the genes wee1+, cdc2+, cdc25+, and sep1+ form a regulatory link between the initiation of mitosis and the initiation of cell division.

Actins↗
PubMed1994

suGF1 binds in the major groove of its oligo(dG).oligo(dC) recognition sequence and is excluded by a positioned nucleosome core.

We have elsewhere reported the purification of a poly(dG).poly(dC)-binding nuclear protein (suGF1) from sea urchin embryos (J. Hapgood and D. Patterton, Mol. Cell. Biol. 14:this issue, 1994). We proposed that suGF1 may be a member of a family of G-string factors involved in developmental gene regulation, possibly via alterations in chromatin structure. In this article, we characterize the binding of purified suGF1 to 11 contiguous Gs in the H1-H4 intergenic region of a sea urchin early histone gene battery in vitro. It is shown that suGF1-DNA binding is dependent on ionic strength and requires divalent cations. Purified suGF1 forms discrete protein-DNA multimers, consistent with suGF1-suGF1 interactions. In a model for the suGF1-DNA complex derived from our footprinting and methylation interference data, suGF1 contacts the Gs in the major groove as well as one of the bordering phosphate backbones. The data are consistent with the direction of curvature of the DNA in the suGF1-DNA complex being the same as that preferred by the free DNA and exhibited by the DNA when bent around a positioned nucleosome core in vitro. However, on the basis of steric considerations, the binding of suGF1 and that of the histone octamer are predicted to be mutually exclusive. We show that suGF1 is indeed unable to bind to the G string when occupied by a histone octamer located in the major in vitro positioning frame in the H1-H4 intergenic region.

Animals↗
PubMed2005

Whole genomewide linkage screen for neural tube defects reveals regions of interest on chromosomes 7 and 10.

Neural tube defects (NTDs) are the second most common birth defects (1 in 1000 live births) in the world. Periconceptional maternal folate supplementation reduces NTD risk by 50-70%; however, studies of folate related and other developmental genes in humans have failed to definitively identify a major causal gene for NTD. The aetiology of NTDs remains unknown and both genetic and environmental factors are implicated. We present findings from a microsatellite based screen of 44 multiplex pedigrees ascertained through the NTD Collaborative Group. For the linkage analysis, we defined our phenotype narrowly by considering individuals with a lumbosacral level myelomeningocele as affected, then we expanded the phenotype to include all types of NTDs. Two point parametric analyses were performed using VITESSE and HOMOG. Multipoint parametric and nonparametric analyses were performed using ALLEGRO. Initial results identified chromosomes 7 and 10, both with maximum parametric multipoint lod scores (Mlod) >2.0. Chromosome 7 produced the highest score in the 24 cM interval between D7S3056 and D7S3051 (parametric Mlod 2.45; nonparametric Mlod 1.89). Further investigation demonstrated that results on chromosome 7 were being primarily driven by a single large pedigree (parametric Mlod 2.40). When this family was removed from analysis, chromosome 10 was the most interesting region, with a peak Mlod of 2.25 at D10S1731. Based on mouse human synteny, two candidate genes (Meox2, Twist1) were identified on chromosome 7. A review of public databases revealed three biologically plausible candidates (FGFR2, GFRA1, Pax2) on chromosome 10. The results from this screen provide valuable positional data for prioritisation of candidate gene assessment in future studies of NTDs.

Chromosomes, Human, Pair 10↗
PubMed1995

Twenty-four cases of the EEC syndrome: clinical presentation and management.

Twenty-four cases of EEC syndrome were identified as part of a nationwide study. Ectodermal dysplasia, by study definition, was present in all cases and hair and teeth were universally affected. Nail dysplasia was present in 19 subjects (79%) and the skin was affected in 21 (87%). The presence of hypohidrosis was not noted as a predominant feature in the syndrome and its occurrence appeared to depend on the presence of all other features. Distal limb defects from simple syndactyly to tetramelic cleft hand and foot were identified, including preaxial anomalies. Orofacial clefting was identified in 14 cases (58%) and lacrimal duct anomaly in 21 (87%). Significant clinical problems encountered were chiefly cosmetic or ophthalmological, but conductive deafness and genitourinary problems in some cases required surgical intervention. Altered self-image was also noted in some cases. Multidisciplinary management is necessary with the early involvement of the clinical geneticist. Developmentally, the EEC syndrome and related disorders represent disorders of ectodermal/mesodermal interaction. Candidate regions include 7q21.3, the "ectrodactyly" locus; other candidates include developmental genes implicated in the ectodermal/mesodermal interactive process.

Abnormalities, Multiple↗
PubMed1994

The germline: familiar and newly uncovered properties.

Transplantations of both Drosophila pole cells and mouse primordial germ cells suggest that the pregonadal germline of these two organisms is not pluripotent. In mouse PGCs, however, the potential for activating pluripotency is clearly present, as seen in the relative case of deriving EG cells from migratory-stage PGCs. EG cells are derived from altering the in vitro growth conditions of PGCs by the addition of one factor. Conceivably, straying of PGCs in vivo could also lead to novel fates if they migrated into a suitable environment. Aberrant PGC migration underlies models for the origin of several tumor types. How are migratory-stage PGCs prevented from adopting alternative fates in wild-type development? One solution is to link accurate migration into the gonads with germ cell survival. One mechanism of accomplishing this is through the action of pleiotrophic factors such as Steel. Steel is both a proliferation and migration factor; sterility in Steel mutants is due to poor germ cell survival and improper migration. Networking of migratory PGCs is another mechanism to reduce the chances of individual germ cells straying from the migration path. Postmigratory germ cells apparently undergo another restriction on potency--novel imprinting. Assuming that EG methylation profiles accurately reflect modifications made in their founder PGCs, then "erased" pluripotent EG lines suggest that PGCs can be diverted from the germline lineage. Direct assays on PGCs show that the unmethylated phenotype at Igf2r region 2 is characteristic of late germ cells. The maintenance of germline-like methylation with a switch in PGC fate is somewhat analogous to the situation in lag mutants from Volvox, which retain large gonidial-sized cells that can nevertheless initiate somatic differentiation. Just as it is not possible to readjust cell size with a subsequent change in gonidial differentiation, it may be difficult, without gametogenesis, to reimpose methylation modifications once they have been erased. In addition, the methylation status of some sites/loci may be inconsequential to developmental gene activity in germ cells or EG cells. Recent studies indicate that the methylation imprint at Igf2r is not interpreted at functional level until embryogenesis (51). In summary, we have reviewed some distinctive properties of the development of germ cells, from their early segregation, mitotic and meiotic profile, sex determination, to their migration and sequestration into gonads. Some constraints on development of the germline likely serve to maintain its integrity until maturation, when the gametic genomes must be capable of initiating embryonic development. To accomplish this ultimate goal, germ cells in some organisms may retain a bias towards pluripotency throughout development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2004

Signaling in myxobacteria.

Myxobacteria use soluble and cell-contact signals during their starvation-induced formation of fruiting bodies. These signals coordinate developmental gene expression with the cell movements that build fruiting bodies. Early in development, the quorum-sensing A-signal in Myxococcus xanthus helps to assess starvation and induce the first stage of aggregation. Later, the morphogenetic C-signal helps to pattern cell movement and shape the fruiting body. C-signal is a 17-kDa cell surface protein that signals by contact between the ends of two cells. The number of C-signal molecules per cell rises 100-fold from the beginning of fruiting body development to the end, when spores are formed. Traveling waves, streams, and sporulation have increasing thresholds for C-signal activity, and this progression ensures that spores form inside fruiting bodies.

Myxococcus xanthus↗
PubMed1999

Maldescendus testis.

Maldescendus testis is a common congenital abnormality occurring in 2-5% of full-term boys at birth in the Western countries. By 3 months of age, the incidence rate spontaneously reduces to 1-2% in this group. The etiology of the disorder is not known, but normal hypothalamo-pituitary-gonadal axis is usually a prerequisite for normal descent of the testes. Abnormal sexual differentiation is associated with maldescent. However, the majority of boys with maldescended testes show no endocrine abnormalities after birth. Several defects in developmental genes, such as homeobox genes and Insl3, have been described to cause cryptorchidism in mice, and disturbances in the regulation of these genes or their mutations may explain etiology of a large part of human testicular maldescent in the future. Increased degeneration of germ cells can be observed in undescended testes after the first year, and therefore early treatment is recommended. Surgical treatment is the most effective and reliable method to bring testes into the scrotum, but hormone treatment with either hCG or GnRH analogues can be considered, particularly in cases where testes can be palpated in high scrotal position. The efficacy of hormone treatment is less than 20% and depends on the initial location of the testis. Nonpalpable testes rarely descend with hormone treatment. Both surgery and hormone treatment can have untoward effects. Treatment with hCG has been associated with an inflammation-like reaction in the testes and an increased rate of apoptosis of germ cells leading to a reduced adult size of the testes. Vascular complications can occur during surgery, particularly in staged orchidopexies. Men with a history of undescended testis have an increased risk of testicular cancer. Impaired fertility is another long-term risk associated to maldescended testes. Fertility potential may be improved by early treatment. Although our knowledge on cryptorchidism has increased considerably during the last decades, many questions remain to be answered: Is the incidence rate increasing? What is causing maldescent? Do hormones have any role in the treatment?

Animals↗
PubMed2002

Identification and characterization of murine Brunol4, a new member of the elav/bruno family.

RNA-binding proteins are involved in post-transcriptional processes like mRNA stabilization, post-transcriptional modification, and transport and have been suggested to play an important role in developmental gene regulation. We report here the cloning and characterization of Brunol4, a novel mouse cDNA closely related to the elav-type family of genes encoding for RNA-binding proteins and a subfamily recently named after the bruno gene of Drosophila. Murine Brunol4 is localized near the centromere of chromosome 18. The cDNA sequence of Brunol4 is separated by 12 introns and the size of Brunol4 may be around 250 kb due to the large size of several introns. Brunol4 expression is detectable in the developing embryo and, later on becomes mainly restricted to cerebral structures, in particular the cerebellum where it persists in the adult organism. We predict a role of Brunol4 and the respective human homologue in differentiation and maintenance of neuronal structures.

Animals↗
PubMed2006

The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina)--phenotypic manifestations and genetic approaches.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome affects at least 1 out of 4500 women and has for a long time been considered as a sporadic anomaly. Congenital absence of upper vagina and uterus is the prime feature of the disease which, in addition, is often found associated with unilateral renal agenesis or adysplasia as well as skeletal malformations (MURCS association). The phenotypic manifestations of MRKH overlap various other syndromes or associations and thus require accurate delineation. Since MRKH manifests itself in males, the term GRES syndrome (Genital, Renal, Ear, Skeletal) might be more appropriate when applied to both sexes. The MRKH syndrome, when described in familial aggregates, seems to be transmitted as an autosomal dominant trait with an incomplete degree of penetrance and variable expressivity. This suggests the involvement of either mutations in a major developmental gene or a limited chromosomal deletion. Until recently progress in understanding the genetics of MRKH syndrome has been slow, however, now HOX genes have been shown to play key roles in body patterning and organogenesis, and in particular during genital tract development. Expression and/or function defects of one or several HOX genes may account for this syndrome.

Abnormalities, Multiple↗
PubMed2004

Pancreatic lipase and its related protein 2 are regulated by dietary polyunsaturated fat during the postnatal development of rats.

The developmental gene expression of pancreatic lipase (PL) and its related proteins (PLRP1 and PLRP2) is anticoordinate. It is unknown whether dietary fat regulates the expression of these proteins in the preweanling stage. For determining the regulation of development and diet on PL, PLRP1, and PLRP2 as early as the suckling period, pregnant (Sprague-Dawley) rats consumed from day 15 (d15) of pregnancy through d9 of lactation a purified low (11% of energy) safflower oil diet [low-fat (LF)]. From d9 of lactation, dams and their respective pups were fed LF, medium-fat (MF; 40% of energy), or high-fat (HF; 67% of energy) safflower oil diets to d56. Milk fatty acid content had 15- to 100-fold less C:10 and 2.6- to 3.3-fold more C18:2 in MF and HF groups. Diet (LF < MF = HF; P < 0.002), postnatal development (d15 < d21 < d28 = d56; P < 0.001), and interaction of diet x development significantly affected PL activity starting as early as d15. PL mRNA levels showed a parallel effect of diet (LF < HF = MF; P < 0.013) and development (P < 0.001). Both PLRP1 and PLRP2 mRNA levels were significantly affected by development (P < 0.001) and had an anticoordinate pattern compared with PL expression (d15 > d21 > d28). Reported for the first time is the significant down-regulation of PLRP2 mRNA levels by high polyunsaturated fat in suckling (d15) rats. In conclusion, PL and PLRP2 gene expression is regulated anticoordinately by the amount of dietary polyunsaturated fat starting as early as the preweanling phase of development.

Animals↗