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PubMed2006

Characterization of low phosphorus insensitive mutants reveals a crosstalk between low phosphorus-induced determinate root development and the activation of genes involved in the adaptation of Arabidopsis to phosphorus deficiency.

Low phosphorus (P) availability is one of the most limiting factors for plant productivity in many natural and agricultural ecosystems. Plants display a wide range of adaptive responses to cope with low P stress, which generally serve to enhance P availability in the soil and to increase its uptake by roots. In Arabidopsis (Arabidopsis thaliana), primary root growth inhibition and increased lateral root formation have been reported to occur in response to P limitation. To gain knowledge of the genetic mechanisms that regulate root architectural responses to P availability, we designed a screen for identifying Arabidopsis mutants that fail to arrest primary root growth when grown under low P conditions. Eleven low phosphorus insensitive (lpi) mutants that define at least four different complementation groups involved in primary root growth responses to P availability were identified. The lpi mutants do not show the typical determinate developmental program induced by P stress in the primary root. Other root developmental aspects of the low P rescue system, including increased root hair elongation and anthocyanin accumulation, remained unaltered in lpi mutants. In addition to the insensitivity of primary root growth inhibition, when subjected to P deprivation, lpi mutants show a reduced induction in the expression of several genes involved in the P starvation rescue system (PHOSPHATE TRANSPORTER 1 and 2, PURPLE ACID PHOSPHATASE 1, ACID PHOSPHATASE 5, and INDUCED BY PHOSPHATE STARVATION 1). Our results provide genetic support for the role of P as an important signal for postembryonic root development and root meristem maintenance and show a crosstalk in developmental and biochemical responses to P deprivation.

Adaptation, Physiological↗

PubMed2006

Molecular mechanisms of pituitary differentiation and regulation: implications for hormone deficiencies and hormone resistance syndromes.

During the last century, the questions posed by scientists and clinicians on pituitary function have led to new concepts about the mechanisms of hormone action and cell differentiation. In particular, the advent of molecular genetics and the cloning of pituitary hormone coding genes followed by discovery of their regulators during the last 20 years has provided tremendous insight into the pathophysiological bases of hormone deficit and excess, as well as offering novel therapeutic opportunities. Most insight was gained through the identification of transcription factors that control the program of pituitary organogenesis and cell differentiation; it is indeed the normal developmental program controlled by these transcriptional regulators that is perturbed in inherited forms of hormone deficiency. This review will summarize our current understanding of these processes and their implications for hormone deficiency and hormone resistance syndromes from a developmental perspective.

Adrenocorticotropic Hormone↗

PubMed1998

The transcriptional program of sporulation in budding yeast.

Diploid cells of budding yeast produce haploid cells through the developmental program of sporulation, which consists of meiosis and spore morphogenesis. DNA microarrays containing nearly every yeast gene were used to assay changes in gene expression during sporulation. At least seven distinct temporal patterns of induction were observed. The transcription factor Ndt80 appeared to be important for induction of a large group of genes at the end of meiotic prophase. Consensus sequences known or proposed to be responsible for temporal regulation could be identified solely from analysis of sequences of coordinately expressed genes. The temporal expression pattern provided clues to potential functions of hundreds of previously uncharacterized genes, some of which have vertebrate homologs that may function during gametogenesis.

Animals↗

PubMed2005

Fibroblast growth factor 2 negatively regulates the induction of neuronal progenitors from neural stem cells.

Fibroblast growth factor 2 (FGF2) exhibits pleiotropic functions during embryogenesis. In neural development, both pro- and antineurogenic activities of FGF2 have been described in the differentiation of neuronal progenitors into postmitotic neurons. We used cultured neural stem cells (NSCs) derived from rat embryonic day 14.5 cortex to determine the FGF2 effect on the induction of early neuronal progenitors. Our data showed that the presence of FGF2 during serum-induced differentiation of NSCs reduced the number of Tuj1(+) neurons. A bromodeoxyuridine (BrdU)/Tuj1 double-labeling assay and expression analyses of the pro- and antineurogenic basic helix-loop-helix (bHLH) factors showed that FGF2 blocked the generation of early neuronal progenitors, but not the cell-cycle exit of dividing neurons. This negative regulation of neuronal induction by FGF2 was associated with the persistent expression of an antineurogenic bHLH, hairy and enhancer of split (HES)-1. A gene-profiling study demonstrated that the developmental programs underlying neuronal differentiation were altered as a whole and identified several developmentally regulated, neural-enriched genes. This work shows that FGF2 exerts an antineurogenic effect during the developmental window when neuronal progenitors are first induced from NSCs. It also provides a novel experimental system that can be used to prospectively identify genes expressed at different stages of neuronal differentiation.

Animals↗

PubMed1998

A developmentally regulated kinesin-related motor protein from Dictyostelium discoideum.

The cellular slime mold Dictyostelium discoideum is an attractive system for studying the roles of microtubule-based motility in cell development and differentiation. In this work, we report the first molecular characterization of kinesin-related proteins (KRPs) in Dictyostelium. A PCR-based strategy was used to isolate DNA fragments encoding six KRPs, several of which are induced during the developmental program that is initiated by starvation. The complete sequence of one such developmentally regulated KRP (designated K7) was determined and found to be a novel member of the kinesin superfamily. The motor domain of K7 is most similar to that of conventional kinesin, but unlike conventional kinesin, K7 is not predicted to have an extensive alpha-helical coiled-coil domain. The nonmotor domain is unusual and is rich in Asn, Gln, and Thr residues; similar sequences are found in other developmentally regulated genes in Dictyostelium. K7, expressed in Escherichia coli, supports plus end-directed microtubule motility in vitro at a speed of 0.14 micron/s, indicating that it is a bona fide motor protein. The K7 motor is found only in developing cells and reaches a peak level of expression between 12 and 16 h after starvation. By immunofluorescence microscopy, K7 localizes to a membranous perinuclear structure. To examine K7 function, we prepared a null cell line but found that these cells show no gross developmental abnormalities. However, when cultivated in the presence of wild-type cells, the K7-null cells are mostly absent from the prestalk zone of the slug. This result suggests that in a population composed largely of wild-type cells, the absence of the K7 motor protein interferes either with the ability of the cells to localize to the prestalk zone or to differentiate into prestalk cells.

Amino Acid Sequence↗

PubMed2004

Expression profiling in Medicago truncatula identifies more than 750 genes differentially expressed during nodulation, including many potential regulators of the symbiotic program.

In this study, we describe a large-scale expression-profiling approach to identify genes differentially regulated during the symbiotic interaction between the model legume Medicago truncatula and the nitrogen-fixing bacterium Sinorhizobium meliloti. Macro- and microarrays containing about 6,000 probes were generated on the basis of three cDNA libraries dedicated to the study of root symbiotic interactions. The experiments performed on wild-type and symbiotic mutant material led us to identify a set of 756 genes either up- or down-regulated at different stages of the nodulation process. Among these, 41 known nodulation marker genes were up-regulated as expected, suggesting that we have identified hundreds of new nodulation marker genes. We discuss the possible involvement of this wide range of genes in various aspects of the symbiotic interaction, such as bacterial infection, nodule formation and functioning, and defense responses. Importantly, we found at least 13 genes that are good candidates to play a role in the regulation of the symbiotic program. This represents substantial progress toward a better understanding of this complex developmental program.

Biological Transport↗

PubMed2006

Prevalence of four developmental disabilities among children aged 8 years--Metropolitan Atlanta Developmental Disabilities Surveillance Program, 1996 and 2000.

PROBLEM/CONDITION: In the United States, developmental disabilities affect approximately 17% of children aged <18 years, resulting in substantial financial and social costs. REPORTING PERIOD: 1996 and 2000. DESCRIPTION OF SYSTEM: The Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) monitors the occurrence of mental retardation, cerebral palsy, hearing loss, vision impairment, and autism spectrum disorders among children aged 8 years in the five-county metropolitan Atlanta area (Clayton, Cobb, DeKalb, Fulton, and Gwinnett). MADDSP uses a multiple source ascertainment methodology. RESULTS: During 1996, the prevalence of mental retardation was 15.5 per 1,000 children aged 8 years; it decreased to 12.0 per 1,000 in 2000. The overall prevalence of cerebral palsy was 3.6 per 1,000 in 1996 and 3.1 per 1,000 in 2000. The prevalence of mental retardation and cerebral palsy was highest among males and black children. The prevalence of hearing loss was 1.4 per 1,000 in 1996 and 1.2 per 1,000 in 2000; the prevalence of vision impairment during 1996 was 1.4 per 1,000 and 1.2 per 1,000 in 2000. Minimal differences by study year were observed in the prevalence of all four disabilities when examined by sex, race, and severity. INTERPRETATION: The prevalence of these four select developmental disabilities in MADDSP was higher in 1996 than the annual average prevalence estimates for these disabilities during previous MADDSP study years (1991-1994) study years; the highest increase was observed among children with mental retardation. However, prevalence estimates during 2000 were more consistent with the estimates from the early 1990s. Data from additional surveillance years (2002 and beyond) are needed to determine if the prevalence for 1996 was an anomaly and to continue to monitor trends in the prevalence of developmental disabilities over time. PUBLIC HEALTH ACTIONS: MADDSP data will continue to be used to examine trends in the occurrence of these disabilities over time, facilitate the development and implementation of appropriate intervention programs, and provide a framework for conducting population-based etiologic studies.

Autistic Disorder↗

PubMed1993

Altered gene expression after optic nerve transection: reduced neurofilament expression as a general response to axonal injury.

Previous studies have shown that axonal injury (axotomy) in neurons of the mammalian peripheral nervous system (PNS) results in a recapitulation of the developmental program for cytoskeletal gene expression; these changes include the increased expression of a developmentally regulated isotype of beta-tubulin (class II) and reduced neurofilament (NF) expression. In the present study we examined the abundance of mRNAs encoding the low-molecular-weight NF protein (NF-L) and class II beta-tubulin in RNA purified from the retinae of newborn rats, from the retinae of adult rats at 2, 7, and 14 days after intracranial transection of the ipsilateral optic nerve, and from contralateral control retinae. In order to facilitate comparison with representative PNS neurons, parallel analyses were carried out in axotomized dorsal root ganglion (DRG) sensory neurons. Since NF-L and class II beta-tubulin are neuron-specific proteins, axotomy-induced alterations in the levels of retinal mRNAs encoding these proteins largely reflect corresponding changes in expression by retinal ganglion cell neurons. Comparison of retinal RNA from newborn and adult (70-day-old) animals demonstrated a postnatal increase in NF-L and a decline in class II beta-tubulin mRNAs comparable to those previously described in DRG neurons. Reductions in NF-L mRNA levels were noted in retina at 2, 7, and 14 days after axotomy and in DRG neurons at 7 and 14 days after axotomy. The abundance of class II beta-tubulin mRNAs increased after axotomy in DRG neurons, but not in retina.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2002

Developmental genetics and evolution of symbiotic structures in nitrogen-fixing nodules and arbuscular mycorrhiza.

Genetic and molecular mechanisms of development are compared for two major plant-microbe endosymbioses: N(2)-fixing nodules (with rhizobia or actinomycetes Frankia) and arbuscular mycorrhiza (with Glomales fungi). Development from the primordia formed de novo in root tissues is common for all known types of N(2)-fixing nodules. However, their structure varies greatly with respect to: (i) tissue topology (location of vascular bundles is peripherical in legumes or central in non-legumes); (ii) position of nodule primordium (inner or outer cortex in legumes, pericycle in non-legumes); (iii) stability of apical meristem (persistent in the indeterminate nodules, transient in the determinate ones). In addition, legumes vary in ability to form compartments harboring endosymbiotic rhizobia and located intercellularly (infection threads) and intracellularly (symbiosomes). Using pea (Pisum sativum) symbiotic mutants, the nodule developmental program is dissected into a range of spatially and temporarily differentiated steps comprising four sub-programs (development of endosymbiotic compartments; nodule histogenesis; autoregulation of nodulation; bacteroid differentiation). The developmental mutations are suggested in some cases to reverse the endosymbiotic system into the morphologically simpler forms some of which may correspond to the ancestral stages of nodule evolution. The origin of legume-rhizobial and actinorhizal symbioses is suggested to be based on a set of preadaptations many of which had been evolved in angiosperms during coevolution with arbuscular mycorrhizal fungi (e.g., inter- and intracellular maintenance of symbionts, their control via defence-like reactions and recognition of chitin-like molecules). An analysis of parallel morphological variation in symbiotic mutants and wild-growing legume species enables us to reconstruct the major stages of evolution for N(2)-fixing symbioses.

Actinomycetales↗

PubMed1999

Use of somatic cell fusion to reprogram globin genes.

The developmental phenomenon of hemoglobin switching occurs in all classes of vertebrates and is due to differential regulation of divergent globin genes which are arranged in chromosomally clustered families. By fusing erythroid cells of different developmental programs, it has been shown that erythroid nuclei of either early or late developmental stage can be reprogrammed, i.e. the gene switch can be reversed in adult erythroid nuclei and/or prematurely-induced in fetal/embryonic erythroid nuclei. Experiments with heterokaryons demonstrate that the reprogramming is due to trans-acting factors that are developmental-stage-specific. These results suggest the feasibility of using fusisome-carried sets of nuclear factors to reprogram somatic cells.

Animals↗

PubMed2006

Deciphering the regulatory mechanisms of abiotic stress tolerance in plants by genomic approaches.

Environmental constraints that include abiotic stress factors such as salt, drought, cold and extreme temperatures severely limit crop productivity. Improvement of crop plants with traits that confer tolerance to these stresses was practiced using traditional and modern breeding methods. Molecular breeding and genetic engineering contributed substantially to our understanding of the complexity of stress response. Mechanisms that operate signal perception, transduction and downstream regulatory factors are now being examined and an understanding of cellular pathways involved in abiotic stress responses provide valuable information on such responses. This review presents genomic-assisted methods which have helped to reveal complex regulatory networks controlling abiotic stress tolerance mechanisms by high-throughput expression profiling and gene inactivation techniques. Further, an account of stress-inducible regulatory genes which have been transferred into crop plants to enhance stress tolerance is discussed as possible modes of integrating information gained from functional genomics into knowledge-based breeding programs. In addition, we envision an integrative genomic and breeding approach to reveal developmental programs that enhance yield stability and improve grain quality under unfavorable environmental conditions of abiotic stresses.

Adaptation, Physiological↗

PubMed1997

Role of imprinting in abnormal human development.

Parental-specific differences in the expression of certain genes (imprinting), may be implicated in the pathogenesis of anomalous gestations, but only a minority manifest themselves as malformation syndromes. Delayed or lost gestations are much more frequent sequelae, as are those disorganized to such an extent that they are usually classified as neoplastic rather than developmental processes. Expression levels from imprinted loci are dependent not only on the number of genomic alleles present and their structural integrity, but also on their specific parental origin. Anomalous expression of imprinted genes during development is sometimes caused by imbalanced representation of maternal and paternal contributions, 'uniparental disomy'. Uniparental parthenogenetic or androgenetic gestations form ovarian teratomas or complete hydatidiform moles, respectively--examples of an arrested developmental program. Uniparental disomy of individual chromosomes or portions thereof has been associated with developmental delay or gestational loss. The phenotype of hemizygous mutation or deletion of imprinted genes is modified by the parental origin of the mutant copy, with dichotomous syndromes defined by parental inheritance, as in the Prader-Willi and Angelman syndromes. Lastly, failure of the imprinting process itself, 'loss of imprinting', may quantitatively alter expression levels of normally imprinted transforming or tumor-suppressing genes, thereby increasing risk for developmental tumors such as Wilms' tumor or choriocarcinoma.

Abortion, Spontaneous↗

PubMed1984

Transient increase in intracellular pH during Dictyostelium differentiation.

The intracellular pH (pHi) of Dictyostelium discoideum amebae has been determined using the pH-dependent fluorescence of intracellularly trapped fluorescein (Thomas, J. A., R. N. Buschbaum, A. Zimiak, and E. Racker, Biochemistry, 18:2210-2218). The pHi of cells measured 45-60 min after initiation of differentiation was between 6.2 and 6.3. At approximately 2 h into differentiation cells underwent a transient intracellular alkalinization during which the pHi rose to 7.13 (+/- 0.3, n = 4), after which the pHi returned to approximately the original value (6.2-6.4). Cells that were removed from growth medium but were incubated in differentiation medium containing 3% dextrose did not exhibit this transient increase in pHi. The alkalinization event can also be prevented from occurring by differentiation in Na+-free solutions or by the addition of amiloride to sodium-containing buffer solutions, suggesting that the alkalinization is sodium dependent. When the alkalinization was prevented by amiloride treatment, cells did not progress normally into differentiation. This increase in pHi was initiated by the cells 2 h after removal from nutrient medium and it could be inhibited by several treatments that had been observed to delay the differentiation program, suggesting that it plays a major role in the initiation of the developmental program of this organism.

Amiloride↗

PubMed2002

The role of indigenous microflora in the development of murine intestinal fucosyl- and sialyltransferases.

Most enteric bacteria use intestinal brushborder glycoconjugates as their target host cell receptors. It has been postulated that resident microbes regulate specific glycosyltransferases that are responsible for synthesizing brushborder glycoconjugates. To investigate this hypothesis, we measured glycosyltransferase enzyme activities in intestine from different regions of maturing conventional (CONV), germ-free (GF), and ex-germ-free (XGF) mice and compared them to general enzyme markers of gut development, for example, disaccharidases. High alpha2,3/6-Sialyltransferase (ST) activity and low alpha1,2-fucosyltransferase (FT) activities were detected from duodenum to colon in suckling CONV mice, but the relative levels of these activities reversed during the third postnatal wk, rapidly reaching adult levels by the fourth wk. These age-related enzyme changes were significantly attenuated in GF mice, maintaining an immature pattern well past 3 wk. Introduction of gut microflora in GF mice rapidly initiated maturation of glycosyltransferase activity but had no significant affect on developmental programming of dissacharidases. Therefore, in mice, intestinal glycosyltransferase activities are under tissue and developmental control and microflora play a major role in their specific ontogeny but not in overall development. These findings may help explain the regional specificity of commensal bacteria and of enteric pathogens and may also relate age-related changes in microflora to susceptibility to enteropathogens.

Age Factors↗

PubMedDate not supplied

The learning achievement program: fostering student cultural diversity.

As students from minority backgrounds increased to approximately 54% of one university nursing program, faculty were concerned as retention of these students has dramatically declined. In response, the school initiated a project called the Learning Achievement Program, funded by Health Resources and Services Administration, which is a transitional and developmental program for minority and/or disadvantaged students. The authors discuss the program, the challenges faced by students and faculty, and how the Learning Achievement Program influenced the diverse population in the nursing school.

Achievement↗

PubMed2004

Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers.

Identification of common mechanisms underlying organ development and primary tumor formation should yield new insights into tumor biology and facilitate the generation of relevant cancer models. We have developed a novel method to project the gene expression profiles of medulloblastomas (MBs)--human cerebellar tumors--onto a mouse cerebellar development sequence: postnatal days 1-60 (P1-P60). Genomically, human medulloblastomas were closest to mouse P1-P10 cerebella, and normal human cerebella were closest to mouse P30-P60 cerebella. Furthermore, metastatic MBs were highly associated with mouse P5 cerebella, suggesting that a clinically distinct subset of tumors is identifiable by molecular similarity to a precise developmental stage. Genewise, down- and up-regulated MB genes segregate to late and early stages of development, respectively. Comparable results for human lung cancer vis-a-vis the developing mouse lung suggest the generalizability of this multiscalar developmental perspective on tumor biology. Our findings indicate both a recapitulation of tissue-specific developmental programs in diverse solid tumors and the utility of tumor characterization on the developmental time axis for identifying novel aspects of clinical and biological behavior.

Animals↗

PubMedDate not supplied

[Comparative genetics and evolutionary morphology of symbiosis formed by plants with nitrogen-fixing microbes and endomycorrhizal fungi].

Results of comparative morphological and genetic analyses are described for two major plant-microbe endosymbioses: N2-fixing nodules (with rhizobia or actinomycetes Frankia) and arbuscular mycorrhiza (with Glomales fungi). Development from the primordia formed de novo in root tissues is common for all known types of N2-fixing nodules. However, their structure varies greatly with respect to: (i) tissue topology (location of vascular bundles is peripheral in legumes but central in non-legumes); (ii) position of nodule primordium (inner or outer cortex in legumes, whereas pericycle in non-legumes); (iii) stability of apical meristem (persistent in the indeterminate nodules, transient in the determinate ones). In addition, legumes vary in ability to form compartments harboring endosymbiotic rhizobia that can be located intercellularly (infection threads) and intracellularly (symbiosomes). Using pea (Pisum sativum) symbiotic mutants, the nodule developmental program is dissected into a range of spatially and temporarily differentiated steps composing four sub-programs (development of endosymbiotic compartments; nodule histogenesis; autoregulation of nodulation; bacteroid differentiation). The developmental mutations are suggested in some cases to reverse the endosymbiotic system into the morphologically simpler forms some of which may correspond to the ancestral stages of nodule evolution. Origination of legume-rhizobial and actinorhizal symbioses is suggested to be based on a set of preadaptations many of which had been evolved in angiosperms during coevolution with arbuscular mycorrhizal fungi (e.g. inter- and intracellular maintenance of symbionts, their control via defence-like reactions and recognition of chitin-like molecules). Analysis of parallel morphological variation in symbiotic mutants and wild-growing legume species enables us to reconstruct the major stages of evolution for N2-fixing symbioses. This evolution proceeded to a sufficient degree independently from the basic physiological function of nodules (symbiotic N2-fixation) and possibly a recruiting of plant genes that initially fulfilled various "non-symbiotic" functions into the genetic networks monitoring plant-microbe interactions.

Bacterial Physiological Phenomena↗

PubMed2003

Heat shock proteins in mammalian development.

Mammalian development follows a defined but adjustable program, depending on the plasticity of embryonic cells 'response to environmental changes. Heat shock proteins (Hsp) are integral part of this developmental program and gene targeting experiments have started to unravel developmental processes, which exhibit specific requirements for Hsps (e.g. Hsp70.2 for spermatogenesis). In the present paper, we will review available data on Hsp function and discuss the roles of heat shock factors (HSF), their major regulators, in mammalian development.

Animals↗