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PubMed1997

A novel homologue of the prokaryotic htrA gene is differentially expressed in the alga Haematococcus pluvialis following stress.

The alga Haematococcus pluvialis is able to respond to environmental stress by changing from the motile, vegetative green cell form to red stationary aplanospores. This differentiation program is accompanied by dramatic morphological changes that must result, at least in part, from differential gene expression. To begin to identify genes that are differentially expressed as a response to stress, we applied the differential display technique to identify and isolate differentially expressed RNA sequences. Here we report on the isolation and characterization of one such RNA sequence that codes for Haematococcus htrA, a member of a heat shock serine protease family previously described only in prokaryotes. Interestingly, database searches of mouse and human cDNA sequences showed that a previously unreported homologue is also found in a number of tissues. htrA mRNA was not detectable in vegetative cells, but was found at high levels in developing aplanospores. Evidence presented suggests that RNA transcripts encoding this protein are differentially spliced, and that the different splice products are differentially expressed during the developmental process. These experiments provide the groundwork upon which the developmental program of H. pluvialis can be investigated. In addition, they indicate that the htrA family of heat shock serine proteases may play an important role in stress response in higher organisms as well as in bacteria.

Amino Acid Sequence↗

PubMed2003

Segmentation: mono- or polyphyletic?

Understanding the evolutionary origins of segmented body plans in the metazoa has been a long-standing fascination for scientists. Competing hypotheses explaining the presence of distinct segmented taxa range from the suggestion that all segmentation in the metazoa is homologous to the proposal that segmentation arose independently many times, even within an individual clade or species. A major new source of information regarding the extent of homology vs. homoplasy of segmentation in recent years has been an examination of the extent to which molecular mechanisms underlying the segmentation process are conserved, the rationale being that a shared history will be apparent by the presence of common molecular components of a developmental program that give rise to a segmented body plan. There has been substantial progress recently in understanding the molecular mechanisms underlying the segmentation process in many groups, specifically within the three overtly segmented phyla: Annelida, Arthropoda and Chordata. This review will discuss what we currently know about the segmentation process in each group and how our understanding of the development of segmented structures in distinct taxa have influenced the hypotheses explaining the presence of a segmented body plan in the metazoa.

Animals↗

PubMed1991

Thyroid hormone regulation of Na,K-ATPase subunit-mRNA expression in neonatal rat myocardium.

Regulation of Na,K-ATPase mRNA alpha isoform and mRNA beta expression by thyroid hormone (T3) in neonatal rat myocardium was examined. In euthyroid neonates between ages of 2 and 5 days, mRNA alpha 1, mRNA alpha 3, and mRNA beta 1 abundances were nearly constant while mRNA alpha 2 was undetectable. During the interval between postnatal days 5 and 15, mRNA alpha 3 decreased to negligible levels and mRNA alpha 2 became expressed and increased in abundance to account for approximately 20% of the mRNA alpha pool by the 15th postnatal day. To examine the effect of T3 on this developmental program, neonates were injected with 75 micrograms T3/100 g body weight or diluent alone on the second and third postnatal days and myocardial Na,K-ATPase subunit-mRNA abundances were determined on the third and fourth postnatal days. Because T3 treatment increased the RNA/DNA ratios of myocardial tissue, the subunit-mRNA abundances were normalized per unit DNA. Following 24 and 48 hr of T3 treatment, the abundances of mRNA alpha 1, mRNA alpha 3, and mRNA beta 1 increased, while mRNA alpha 2 continued to remain undetectable during the 2-day interval between the second to fourth postnatal days. It is concluded that T3 augments the abundance of Na,K-ATPase subunit mRNAs that are already being expressed in the neonatal rat myocardium. The results further suggest that T3 does not act as a "molecular switch" in the developmental expression of the mRNA alpha isoforms in rat myocardium during the first four postnatal days.

Analysis of Variance↗

PubMed2006

Expression of LGR7 and LGR8 by neonatal porcine uterine tissues and transmission of milk-borne relaxin into the neonatal circulation by suckling.

Estrogen receptor-dependent organizational events between birth [postnatal day (PND) 0] and PND 14 affect development and function of porcine uterine tissues. Observations that uterotrophic effects of relaxin (RLX) in neonatal gilts were inhibited by the antiestrogen ICI 182,780 suggested that a RLX signaling system, capable of cross-talk with the estrogen receptor, evolves during a critical period for uterine programming (PND 0-14). Objectives were to determine 1) effects of age and estrogen exposure from birth on porcine uterine RLX/insulin-like 3 receptor (LGR7/LGR8) expression and 2) whether milk serves as a natural source of RLX in neonatal pigs. Uterine LGR7/LGR8 expression, detected by RT-PCR and in situ hybridization on PND 0, 7, and 14, was predominantly stromal for LGR7, myometrial for LGR8, and increased with age and after treatment with estradiol valerate (50 microg/kg body weight x d) from birth. Stromal expression of LGR7 was also detected immunohistochemically. Milk RLX concentrations declined (P < 0.001) from 17.3 +/- 1.4 ng/ml (lactation d 0) to 1.7 +/- 0.3 ng/ml (lactation d 14). RLX, present in the serum of nursing pigs on PND 0 and 1, was undetectable before nursing and in neonates fed RLX-free milk replacer for 12 h. Thus, a developmentally regulated, estrogen-sensitive LGR7 and LGR8 receptor system is present in the porcine uterus at birth and may be activated by milk-borne RLX delivered into the circulation during the first 48 h of postnatal life. Maternal lactocrine contributions to the neonatal hormonal milieu could affect the developmental programming of uterine and other somatic tissues.

Animals↗

PubMed2002

ASI1, a gene encoding a novel leucine zipper protein, is induced during development of the macronucleus in Tetrahymena.

Sexual reproduction in the ciliate Tetrahymena follows a complex developmental program involving the sequential regulation of dozens of genes. Genes that are up-regulated during post-zygotic development in Tetrahymena were isolated by subtractive hybridization. Anlagen stage induced gene 1 (ASI1) encodes a 2.8 kb transcript that contains a single intron and is induced during macronuclear development. ASI1 is a single copy gene in both the micronucleus and the macronucleus. It encodes a 95 kDa conceptual protein with a leucine zipper near the amino terminus.

Amino Acid Sequence↗

PubMed2005

Comprehensive interaction map of the Arabidopsis MADS Box transcription factors.

Interactions between proteins are essential for their functioning and the biological processes they control. The elucidation of interaction maps based on yeast studies is a first step toward the understanding of molecular networks and provides a framework of proteins that possess the capacity and specificity to interact. Here, we present a comprehensive plant protein-protein interactome map of nearly all members of the Arabidopsis thaliana MADS box transcription factor family. A matrix-based yeast two-hybrid screen of >100 members of this family revealed a collection of specific heterodimers and a few homodimers. Clustering of proteins with similar interaction patterns pinpoints proteins involved in the same developmental program and provides valuable information about the participation of uncharacterized proteins in these programs. Furthermore, a model is proposed that integrates the floral induction and floral organ formation networks based on the interactions between the proteins involved. Heterodimers between flower induction and floral organ identity proteins were observed, which point to (auto)regulatory mechanisms that prevent the activity of flower induction proteins in the flower.

Arabidopsis↗

PubMed2006

Common critical pathways in embryogenesis and cancer.

Cancer may arise because the developmental programs that create the dramatic alterations in form and structure in embryonic development are potentially corrupted. The cells in our bodies retain memories of these processes and cancer can occur later in life if imperfections occur in the fidelity of these pathways. This article is particularly interested in the phenomenon of epithelial to mesenchymal transition, which occurs in embryogenesis. Also reviewed are the small molecules and pathways that are involved both in homeostasis in adult epithelium and embryogenesis in utero. There are five such pathways in particular selected for review in this article: the Wnt pathway, Hedgehog, Notch, PAR and Bone morphogenetic peptide/TGF beta. These are usually conserved throughout mammalian evolution. Though they have been arbitrarily separated in this article they are not exclusive from one another. Their pathologically altered expression is found especially frequently in childhood tumours where they may recapitulate their developmental role, and in tumours that resemble primitive precursor cells. These pathways are important for selecting cell fates, cellular rearrangements, cytological context and morphologic design in embryology as well as participating in epithelial function in adults.

Animals↗

PubMed1991

Identification of cell-type-specific genes of Volvox carteri and characterization of their expression during the asexual life cycle.

Volvox carteri possesses two morphologically and functionally distinct cell types: somatic cells and gonidia (asexual reproductive cells). To define the developmental programs involved in the differentiation of these two cell types, we have isolated 31 nonhomologous cDNA clones that hybridized to RNAs that were significantly more abundant in one cell type than the other. Details of the cell-type- and stage-specificity of expression of the transcripts detected by these cDNAs (plus five genes previously characterized by others) were examined by Northern-blot analysis. Accumulation patterns for the 19 gonidial transcripts fell into two distinct classes: transcripts of one gene were maximally abundant in very early cleavage, whereas transcripts of the other 18 did not reach maximal abundance until quite late in gonidial development. Similarly, the 12 somatic-cell-specific transcripts fell into two categories: transcripts of 5 "early" somatic genes became abundant soon after the completion of embryogenesis, whereas transcripts of 7 "late" somatic genes were not detected until later developmental stages. Expression of 3 other genes (two involved in flagellar development and one that encodes an extracellular matrix component) was also found to be restricted largely to somatic cells. These studies indicate that phenotypic differences between somatic cells and gonidia can be at least partially explained by differential regulation of RNA accumulation, and that there appear to be multiple patterns of accumulation of cell-type-specific transcripts within each cell type.

Animals↗

PubMed1991

A unique zinc finger protein is associated preferentially with active ecdysone-responsive loci in Drosophila.

Using an immunochemical approach, we have identified a unique antigen, PEP (protein on ecdysone puffs), which is associated in third-instar larvae with the active ecdysone-regulated loci on polytene chromosomes; PEP is not associated with most intermolt puffs and is found on some, but not all, heat shock-induced puffs. The distribution pattern changes with changing puffing patterns in the developmental program. We have screened an expression library and recovered a cDNA clone encoding PEP. PEP possesses multiple potential nucleic acid- and protein- binding regions: a glycine- and asparagine-rich amino terminus, four zinc finger motifs, two very acidic segments, two short basic stretches, and an alanine- and proline-rich carboxyl terminus. The Pep gene maps by in situ hybridization to the cytological locus 74F, adjacent to the early ecdysone-responsive region; however, the gene is not regulated by ecdysone at the level of transcription. The pattern of Pep expression through development suggests that maternal Pep gene transcripts are supplied to the embryo, and that the abundance of Pep gene transcripts decreases to a lower, fairly constant level thereafter. This unusual protein may play a role in the process of gene activation, or possibly in RNA processing, for a defined set of developmentally regulated loci.

Amino Acid Sequence↗

PubMed2005

Control of plant development and gene expression by sugar signaling.

Coordination of development with the availability of nutrients, such as soluble sugars, may help ensure an adequate supply of building materials and energy with which to carry out specific developmental programs. For example, in-vivo and in-vitro experiments suggest that increasing sugar levels delay seed germination and stimulate the induction of flowering and senescence in at least some plant species. Higher sugar concentrations can also increase the number of tubers formed by potatoes and can stimulate the formation of adventitious roots by Arabidopsis. New insights into the mechanisms by which sugar-response pathways interact with other response pathways have been provided by microarray experiments examining sugar-regulated gene expression under different light and nitrogen conditions.

Carbohydrates↗

PubMed2001

Differential transcriptional regulation of individual TCR V beta segments before gene rearrangement.

The promoter sequences of individual murine TCR Vbeta segments are dissimilar, but any functional differences between them are masked after productive gene rearrangement by the dominance of the TCRbeta 3' enhancer. However, thymocytes of recombination-activating gene-2 (Rag2)-deficient mice allow the transcriptional activity of Vbeta promoters to be studied before rearrangement. Here we report that many Vbeta segments are detectably transcribed in Rag2(-/-) thymocytes and that there are significant differences in expression among different Vbeta segments. Primer extension and characterization of cDNA clones from SCID thymocytes suggest that these germline Vbeta transcripts generally use the same start sites as those previously determined in mature T cells. The strength of expression before rearrangement does not correlate with proximity to the known enhancer, because members of the most distal Vbeta cluster (Vbeta2.1, Vbeta1.1, Vbeta4.1) are relatively strongly expressed and more proximal Vbeta segments (Vbeta14.1, Vbeta3.1, Vbeta7.1, Vbeta6.1) are only weakly expressed. Different Vbeta segments also show different developmental programs of activation in different thymocyte subsets, with the Vbeta5.1(L)-8.2(V) spliced transcript expressed earliest as well as most strongly overall. Comparison with Rag(+) MHC class I(-/-) and class II(-/-) thymocytes confirms that many of these expression differences are leveled by rearrangement and/or by beta selection, before MHC-dependent selection. However, the expression pattern of Vbeta2.1 is highly distinctive and includes cell types apparently outside the T lineage, suggesting potential acquisition of specialized roles.

Animals↗

PubMed1998

Thymocyte selection in Vav and IRF-1 gene-deficient mice.

T cells undergo a defined program of phenotypic and genetic changes during differentiation within the thymus. These changes define commitment of T-cell receptor (TCR) gamma delta and TCR alpha beta cells and lineage differentiation into CD4+ T helper and CD8+ cytotoxic T cells. T-cell differentiation and selection in the thymus constitute a tightly co-ordinated multistep journey through a network that can be envisaged as a three-dimensional informational highway made up of stromal cells and extracellular matrix molecules. This intrathymic journey is controlled by information exchange, with thymocytes depending on two-way cellular interactions with thymic stromal cells in order to receive essential signals for maturation and selection. Genetic inactivation of surface receptors, signal transduction molecules, and transcription factors using homologous recombination has provided novel insight into the signaling cascades that relay surface receptor engagement to gene transcription and subsequent progression of the developmental program. In this review we discuss molecular mechanisms of T lymphocyte development in mice that harbour genetic mutations in the guanine nucleotide exchange factor Vav and the interferon regulatory transcription factor 1 (IRF-1). We also propose a novel model of T-cell selection based on TCR alpha chain-directed signals for allelic exclusion and TCR alpha-based selection for single receptor usage.

Alleles↗

PubMed1993

Asymmetric expression of the gyrase B gene from the replication-competent chromosome in the Caulobacter crescentus predivisional cell.

The bacterium Caulobacter crescentus undergoes an asymmetric cell division resulting in the formation of two different daughter cells, a motile swarmer cell and a nonmotile stalked cell. These two cell types differ in their program of gene expression, their ability to replicate DNA, and the physical properties of their nucleoids. We show here that two genes, gyrB (encoding the gyrase B subunit) and orf-1, are specifically transcribed from the chromosome in the portion of the predivisional cell destined for the progeny stalked cell. This is in contrast to a subset of flagellar genes which are transcribed from the chromosome in the incipient swarmer portion of the predivisional cell. gyrB and orf-1 are within a newly identified cluster of genes involved in DNA replication and recombination, including dnaN and recF. The transcription of gyrB and orf1 occurs from the replication-competent chromosome in stalked and predivisional cells and is silenced in swarmer cells. We hypothesize that selective silencing of groups of genes in the chromosomes at the swarmer and stalked poles of the predivisional cell results in the different developmental programs and the difference in replicative ability of the two progeny cells.

Amino Acid Sequence↗

PubMed2003

Expression profiles of novel thyroid hormone-responsive genes and proteins in the tail of Xenopus laevis tadpoles undergoing precocious metamorphosis.

Thyroid hormones (THs) are critical for the growth, development, and homeostasis of many organisms and are necessary for metamorphosis of Xenopus laevis tadpoles. TH-induced metamorphosis requires alterations in the transcriptome and the proteome. However, only a few of the molecular components of this developmental program have been identified and their interrelationship remains unclear. Using a cDNA array comprised of 420 known anuran genes and quantitative PCR, we have identified 93 TH-responsive genes in the tail of premetamorphic tadpoles after exogenous administration of T3. Fifty-three of these mRNA transcripts have not previously been characterized as TH responsive in any species. The gene expression profiles show distinctive temporal patterns with most transcript steady-state levels increasing after induction of metamorphosis. Two-dimensional gel electrophoresis of total protein extracts from the tail shows changes in steady-state levels of many proteins after T3 treatment. Of the up-regulated proteins, 10 were identified by peptide mass mapping. These data identify potential components involved in the regulation of Xenopus tail regression by T3 and begin to address a critical question regarding the interrelationship between the transcriptome and the proteome in TH-dependent developmental processes.

Animals↗

PubMed1984

Fatty involution of bone marrow in rabbits.

The developmental pattern of red and yellow bone marrow was studied in rabbits of different ages from newborn to 6 months of age. At birth no adipose cells were seen in any of the marrow cavities. Most bones were still developing and marrow cavities were relatively limited. Nonetheless a distinct difference in the cellularity of marrow in the trunk versus limb bones was noted, the latter being significantly less cellular. Adipose cells began to develop at 2 weeks of age and proceeded so that the adult pattern of red and yellow marrow was fully established by 4 months. The development of adipose cells occurred in both trunk and limb bones; the magnitude of the process, however, was considerably greater in the limb bones. Adipocyte precursors may be present in the marrow at birth with a differential distribution in the areas of prospective red and yellow marrow. Thus, fatty involution of marrow appears to be a programmed developmental event.

Adipose Tissue↗

PubMedDate not supplied

Ectopic dendrite initiation: CNS pathogenesis as a model of CNS development.

The neuronal storage diseases are a rare group of disorders with profound clinical consequences including severe mental retardation and death in early childhood. A subset of these disorders, those with elevated levels of GM2 ganglioside, are further characterized by the reinitiation of primary dendrites on mature cortical neurons. These ectopic dendrites are unusual as primary dendrite initiation is normally confined to a narrow developmental window. Thus, ectopic dendritogenesis appears to be a recapitulation of the normal developmental program temporally displaced. Consequently, understanding ectopic dendritogenesis should offer insights into both the pathogenesis of the neuronal storage diseases as well as mechanisms of normal CNS development. Using a feline model of GM2 gangliosidosis, we compared patterns of gene expression in normal newborn and mature diseased animals (both undergoing active primary dendritogenesis) with normal, mature controls (where primary dendritogenesis has ceased). From this work, we have identified two genes that appear to function in primary dendrite initiation. One, tomoregulin, is an integral membrane protein with both EGF- and follistatin-like motifs in its extracellular domain. The second, Tristanin, is a member of the positive regulatory domain (PRD) family of a zinc-finger transcription factors. Both genes are up regulated in the disease state, and both show a shift in their intracellular location to the nucleus in diseased animals that is not observed in age matched controls. In normal mouse brain, tomoregulin and Tristanin reveal developmental patterns consistent with a role in dendrite initiation and show changes in subcellular localization similar to that observed in the cat.

Animals↗

PubMed2006

Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor.

The cellular and molecular events underlying the formation and differentiation of mesoderm to derivatives such as blood are critical to our understanding of the development and function of many tissues and organ systems. How different mesodermal populations are set aside to form specific lineages is not well understood. Although previous genetic studies in the mouse embryo have pointed to a critical role for the homeobox gene Mix-like (mMix) in gastrulation, its function in mesoderm development remains unclear. Hematopoietic defects have been identified in differentiating embryonic stem cells in which mMix was genetically inactivated. Here we show that conditional induction of mMix in embryonic stem cell-derived embryoid bodies results in the early activation of mesodermal markers prior to expression of Brachyury/T and acceleration of the mesodermal developmental program. Strikingly, increased numbers of mesodermal, hemangioblastic, and hematopoietic progenitors form in response to premature activation of mMix. Differentiation to primitive (embryonic) and definitive (adult type) blood cells proceeds normally and without an apparent bias in the representation of different hematopoietic cell fates. Therefore, the mouse Mix gene functions early in the recruitment and/or expansion of mesodermal progenitors to the hemangioblastic and hematopoietic lineages.

Animals↗

PubMed2001

Requirement for Pbx1 in skeletal patterning and programming chondrocyte proliferation and differentiation.

Pbx1 and a subset of homeodomain proteins collaboratively bind DNA as higher-order molecular complexes with unknown consequences for mammalian development. Pbx1 contributions were investigated through characterization of Pbx1-deficient mice. Pbx1 mutants died at embryonic day 15/16 with severe hypoplasia or aplasia of multiple organs and widespread patterning defects of the axial and appendicular skeleton. An obligatory role for Pbx1 in limb axis patterning was apparent from malformations of proximal skeletal elements, but distal structures were unaffected. In addition to multiple rib and vertebral malformations, neural crest cell-derived skeletal structures of the second branchial arch were morphologically transformed into elements reminiscent of first arch-derived cartilages. Although the skeletal malformations did not phenocopy single or compound Hox gene defects, they were restricted to domains specified by Hox proteins bearing Pbx dimerization motifs and unaccompanied by alterations in Hox gene expression. In affected domains of limbs and ribs, chondrocyte proliferation was markedly diminished and there was a notable increase of hypertrophic chondrocytes, accompanied by premature ossification of bone. The pattern of expression of genes known to regulate chondrocyte differentiation was not perturbed in Pbx1-deficient cartilage at early days of embryonic skeletogenesis, however precocious expression of Col1a1, a marker of bone formation, was found. These studies demonstrate a role for Pbx1 in multiple developmental programs and reveal a novel function in co-ordinating the extent and/or timing of proliferation with terminal differentiation. This impacts on the rate of endochondral ossification and bone formation and suggests a mechanistic basis for most of the observed skeletal malformations.

Age Factors↗