Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genes, Developmental”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

Three amphioxus Wnt genes (AmphiWnt3, AmphiWnt5, and AmphiWnt6) associated with the tail bud: the evolution of somitogenesis in chordates.

The amphioxus tail bud is similar to the amphibian tail bud in having an epithelial organization without a mesenchymal component. We characterize three amphioxus Wnt genes (AmphiWnt3, AmphiWnt5, and AmphiWnt6) and show that their early expression around the blastopore can subsequently be traced into the tail bud; in vertebrate embryos, there is a similar progression of expression domains for Wnt3, Wnt5, and Wnt6 genes from the blastopore lip (or its equivalent) to the tail bud. In amphioxus, AmphiWnt3, AmphiWnt5, and AmphiWnt6 are each expressed in a specific subregion of the tail bud, tentatively suggesting that a combinatorial code of developmental gene expression may help generate specific tissues during posterior elongation and somitogenesis. In spite of similarities within their tail buds, vertebrate and amphioxus embryos differ markedly in the relation between the tail bud and the nascent somites: vertebrates have a relatively extensive zone of unsegmented mesenchyme (i.e., presomitic mesoderm) intervening between the tail bud and the forming somites, whereas the amphioxus tail bud gives rise to new somites directly. It is likely that presomitic mesoderm is a vertebrate innovation made possible by developmental interconversions between epithelium and mesenchyme that first became prominent at the dawn of vertebrate evolution.

Animals↗

Tuareg, a novel miniature-inverted repeat family of pearl millet (Pennisetum glaucum) related to the PIF superfamily of maize.

Miniature-inverted repeat transposable elements (MITEs) are abundantly repeated in plant genomes and are especially found in genic regions where they could contribute regulatory elements for gene expression. We describe with molecular and cytological tools the first MITE family reported in pearl millet: Tuareg. It was initially detected in the pearl millet ortholog of Teosinte-branched1, an important developmental gene involved in the domestication of maize. The Tuareg family was amplified recently in the pearl millet genome and elements were found more abundant in wild than in domesticated plants. We found that they shared similarity in their terminal repeats with the previously described mPIF MITEs and that they are also present in other Pennisetum species, in maize and more distantly related grasses. The Tuareg family may be part of MITEs activated by PIF-like transposases and it could have been mobile since pearl millet domestication.

Base Sequence↗

Vitamin A and embryonic development: an overview.

Vitamin A is an essential micronutrient throughout the life cycle. Its active form, retinoic acid via retinoid receptors, is involved in signal transduction pathways regulating development. Both the lack and excess of vitamin A during embryonic development result in congenital malformations. Approaches to examine the function of vitamin A in embryonic development have included treatment with excess retinoids and the use of retinoid receptor knock-out mice, which have provided important insights into the complexity of the retinoid signaling system. A recently explored model is the retinoid ligand knock-out, i.e., the vitamin A-deficient embryo. Early development can be successfully examined in the vitamin A-deficient avian embryo, in which bioactive retinoids can rescue the deficient genotype as well as phenotype. In this model it has been possible to unequivocally link the physiological function of vitamin A to development of heart, embryonal circulatory and central nervous systems and the regulation of heart asymmetry. Several developmental genes regulated by endogenous vitamin A during early embryogenesis have been identified. Retinoid receptors and their endogenous ligands, the vitamin A-active forms, are present in the early embryo. It is the developmentally regulated biogeneration of the vitamin A-active forms via distinct spatio-temporal metabolic pathways that is critically linked to the initiation of retinoid signal transduction during embryonic development.

Animals↗

The FruA signal transduction protein provides a checkpoint for the temporal co-ordination of intercellular signals in Myxococcus xanthus development.

During fruiting body morphogenesis in Myxococcus xanthus, the intercellular C-signal induces aggregation, sporulation and developmental gene expression. To understand how a single signal system may induce temporally separated processes, we have focused on the class II gene, which codes for an essential component in the C-signal transduction pathway. We report that class II is identical to fruA and codes for a DNA binding response regulator. Transcription of fruA is developmentally regulated and depends on the early acting intercellular A- and E-signals. However, fruA transcription is independent of C-signal. Rather, genetic evidence suggests that C-signal controls FruA activity post-translationally. Genetic evidence strongly indicates that FruA is activated by phosphorylation. We propose that C-signalling results in the phosphorylation of FruA, thus activating FruA to interact with downstream targets. In the motility branch of the C-signalling pathway, FruA interacts with the Frz motility system; in the sporulation branch, we show that FruA is required for transcription of the sporulation locus devRS. On the basis of the two levels of control of FruA activity, we propose that FruA serves as a control point for the temporal co-ordination of intercellular signals during M. xanthus development.

Amino Acid Sequence↗

Transdifferentiation induced by gene transfer.

While for many tissues the differentiation process is well characterized, little is known about 'master switch' genes determining a specific differentiation pathway and having the potential to induce this process in a cell designed for a different differentiation pathway. Based on heterokaryon and 5-aza-cytidine-induced hypomethylation experiments, the muscle determination gene MyoD1 was identified and isolated, which was shown to induce myogenic differentiation even in cells of ectodermal lineage. Since transdifferentiation studies could also be performed in drosophila in vivo by 'false' expression of developmental genes, it is tempting to speculate that experimentally induced transdifferentiation mimics processes during embryonic development and tissue maturation.

Animals↗

Cloning and characterization of a Schizophyllum gene with A beta 6 mating-type activity.

The A-pathway of development in the basidiomycete fungus Schizophyllum commune may be activated by either of two mating-type loci, A alpha and A beta. A alpha consists of two multiallelic genes, Y and Z. Y contains a putative homeodomain; Z contains a homeodomain-related region. Non-self combinations of Y and Z form heteromultimers which are thought to be transcription factors of developmental genes. To more completely understand A-regulated development it is necessary to address the issue of functional redundancy, i.e., how do two different mating loci, A alpha and A beta, both manage to regulate the same pathway. Here we report the structure of a gene with A beta 6 activity. This gene, denoted A beta V6, encodes a deduced polypeptide of 640 amino-acids with a homeodomain motif. V6 also contains a 20-amino acid sequence that is conserved in A alpha Y1, Y3 and Y4. Except for the homeodomain and the conserved sequence, the deduced V6 polypeptide shows no significant identity to A alpha Y, A alpha Z, or other known proteins. The presence of a homeodomain suggests that V, like Y and Z, may be a regulatory protein for genes in the A-pathway. Thus while A alpha and A beta encode different proteins, the general mechanism by which A alpha and A beta components signal A-regulated development may be similar.

Amino Acid Sequence↗

RNA interference-inducing hairpin RNAs in plants act through the viral defence pathway.

RNA interference (RNAi) is widely used to silence genes in plants and animals. It operates through the degradation of target mRNA by endonuclease complexes guided by approximately 21 nucleotide (nt) short interfering RNAs (siRNAs). A similar process regulates the expression of some developmental genes through approximately 21 nt microRNAs. Plants have four types of Dicer-like (DCL) enzyme, each producing small RNAs with different functions. Here, we show that DCL2, DCL3 and DCL4 in Arabidopsis process both replicating viral RNAs and RNAi-inducing hairpin RNAs (hpRNAs) into 22-, 24- and 21 nt siRNAs, respectively, and that loss of both DCL2 and DCL4 activities is required to negate RNAi and to release the plant's repression of viral replication. We also show that hpRNAs, similar to viral infection, can engender long-distance silencing signals and that hpRNA-induced silencing is suppressed by the expression of a virus-derived suppressor protein. These findings indicate that hpRNA-mediated RNAi in plants operates through the viral defence pathway.

Arabidopsis↗

Autonomous developmental control of human embryonic globin gene switching in transgenic mice.

The mechanisms by which expression of the beta-like globin genes are developmentally regulated are under intense investigation. The temporal control of human embryonic (epsilon) globin expression was analyzed. A 3.7-kilobase (kb) fragment that contained the entire human epsilon-globin gene was linked to a 2.5-kb cassette of the locus control region (LCR), and the developmental time of expression of this construct was studied in transgenic mice. The human epsilon-globin transgene was expressed in yolk sac-derived primitive erythroid cells, but not in fetal liver or bone marrow-derived definitive erythroid cells. The absence of epsilon gene expression in definitive erythroid cells suggests that the developmental regulation of the epsilon-globin gene depends only on the presence of the LCR and the epsilon-globin gene itself (that is, an autonomous negative control mechanism). The autonomy of epsilon-globin gene developmental control distinguishes it from the competitive mechanism of regulation of gamma and beta-globin genes, and therefore, suggests that at least two distinct mechanisms function in human hemoglobin switching.

Animals↗

Human beta-globin locus control region: analysis of the 5' DNase I hypersensitive site HS 2 in transgenic mice.

The human beta-globin locus control region (LCR) is essential for high-level expression of human epsilon-, gamma-, and beta-globin genes. Developmentally stable DNase I hypersensitive sites (designated HS) mark sequences within this region that are important for LCR activity. A 1.9-kilobase (kb) fragment containing the 5' HS 2 site enhances human beta-globin gene expression 100-fold in transgenic mice and also confers position-independent expression. To further define important sequences within this region, deletion mutations of the 1.9-kb fragment were introduced upstream of the human beta-globin gene, and the constructs were tested for activity in transgenic mice. Although enhancer activity was gradually lost with deletions of both 5' and 3' sequences, a 373-base-pair (bp) fragment retained the ability to confer relative position-independent expression. Three prominent DNase I footprints were observed in this region with extracts from the human erythroleukemia cell line K-562, one of which contained duplicated binding sites for transcription factor AP-1 (activator protein 1). When the 1.9-kb fragment containing an 18-bp deletion of the AP-1 binding sites was tested in transgenic mice, enhancer activity decreased 20-fold but position-independent expression was retained.

Animals↗

Transgenic animals.

The ability to introduce foreign genes into the germ line and the successful expression of the inserted gene in the organism have allowed the genetic manipulation of animals on an unprecedented scale. The information gained from the use of the transgenic technology is relevant to almost any aspect of modern biology including developmental gene regulation, the action of oncogenes, the immune system, and mammalian development. Because specific mutations can be introduced into transgenic mice, it becomes feasible to generate precise animal models for human genetic diseases and to begin a systematic genetic dissection of the mammalian genome.

Animals↗

Mesodermal cell determination and differentiation.

Many in vitro systems have been designed to study the processes governing cell determination and differentiation during development. Mammalian culture systems have been particularly helpful in elucidating the mechanisms regulating gene expression during differentiation in cells of mesodermal origin, namely, myoblasts, preadipocytes, and chondroblasts. Studies have shown that particular cis-acting sequences and trans-acting factors are important in determining tissue-specific and developmental gene expression in these systems. The role of growth factors, oncogenes, and other agents during differentiation has also been examined. Recently four putative muscle determination genes have been isolated and are being characterized. These studies have been useful in postulating models of how development proceeds in vivo and how differentiation and transformation to a neoplastic phenotype may be related.

Adipose Tissue↗

Mutation analysis of the HOX paralogous 4-13 genes in children with acute lymphoid malignancies: identification of a novel germline mutation of HOXD4 leading to a partial loss-of-function.

The molecular basis of susceptibility to childhood malignant hemopathy remains largely unknown. An excess of skeletal congenital anomalies has been reported among children with hematological malignancy and points towards involvement of developmental genes, like those belonging to the HOX gene family. In addition to their role in embryogenesis, HOX transcription factors are known to be regulators of proliferation and differentiation of hematopoietic cells. We aimed to explore the possibility that germline alterations of HOX genes might be involved in childhood acute lymphoid malignancies. A cohort of 86 children diagnosed with acute lymphoid malignancy was studied, 20 of them concurrently presenting a congenital anomaly of the skeleton. First, we screened for nucleotide changes throughout the HOX genes of paralogous groups 4 to 13 in the 20 patients with skeletal defects, following a skeletal phenotype-based strategy. Subsequently, we extended the HOX mutation screening to the other 66 children having a malignant lymphoproliferative disorder, but without skeletal defects. In total, 16 germline mutations were identified. While 13 changes were also observed in healthy controls, three variants were exclusively found in acute lymphoid malignancy cases. These comprised the germline c.242A>T (p.Glu81Val) missense mutation of HOXD4, detected in two children diagnosed with acute lymphoblastic leukemia (ALL). Furthermore, this mutation was found in association with other specific HOX variants of cluster D (2q31-q37), defining a unique haplotype. Functional analysis of the murine Hoxd4 homolog revealed that mutant Hoxd4 protein had lower transcriptional activity than wild-type protein in vitro. The p.Glu81Val mutation of HOXD4 thus results in a partial loss-of-function, which might be involved in childhood ALL.

Adolescent↗

Current efforts in the analysis of RNAi and RNAi target genes.

RNAi is RNA interference by short RNAs. It influences gene-expression by down-regulation of mRNAs, typically by complementarity to the 3' UTR (untranslated region) of the mRNA. microRNAs (miRNAs) are short RNAs acting as natural RNAi. miRNAs mediate down-regulation of many mRNAs from developmental genes and transcription factor genes. Natural examples for this additional level of post-transcriptional control are increasing. Suitable computer-based search strategies for new miRNA candidates include precursor folding as well as different compositional search strategies. Example programs for this are presented. New own and other data are provided for an overview on such strategies. A strategy feasible in plants for miRNA target identification is direct base pairing of miRNAs to potential mRNA target 3' UTRs. Correct identification in animals usually requires comparative genomics and conserved UTR regions pairing to conserved miRNA substructures. A number of example programs and target examples for these tasks are examined. Finally, strategies and programs for artificial gene silencing by designed RNAi are explained.

Animals↗

The 5' part of the human H19 RNA contains cis-acting elements hampering its translatability.

H19 is an imprinted gene developmentally regulated in man and mouse and implicated in various neoplasms. No corresponding protein product has yet been detected, although several open reading frames (ORFs) could be identified along its RNA. The largest ORF found in the human gene could encode a putative 26 kDa protein. We have isolated two H19 cDNAs (AP and ES) that contain this ORF4 and correspond to incomplete copies of the unique 2.3 kb H19 RNA. In transient expression assays, AP was able to synthesize a 26 kDa protein whereas ES was not. With respect to ORF4, ES exhibits a 536 bp long GC-rich 5' untranslated region, whereas AP contains the last 22 nucleotides of this 5'UTR. Using deletions and point mutations, we have found that the length and probably the secondary structure of the 5'UTR strongly hampers the translatability of the RNA. In addition, a potential role of upstream ORFs (uORFs) was detected as stressed by the enhances translation of a construct mutated in uORF3 overlapping ORF4. Interactions between H19 and proteins are indicated by a specific binding between 5'UTR derived RNA segments and two nuclear proteins of about 27 kDa. Our results favor a potential role of these particular structures and binding properties in general trans-regulation of RNA post-transcriptional processes rather than in normal control of H19 mRNA translation.

Animals↗

Low expression of Wnt-5a gene is associated with high-risk neuroblastoma.

Disseminated forms of neuroblastoma (NB), a tumor derived from neuroectodermal tissue, pose a major therapeutic challenge for pediatric oncology. By performing a comparative cDNA array analysis of metastatic neuroblasts versus primary xenograft from the human IGR-N-91 NB model, we were able to identify a set of downregulated developmental genes in metastatic neuroblasts. One of these genes was Wnt-5a, a member of the Wnt signaling pathway, known to be involved in the development of neural crest cells. Since we also found a significant decrease in Wnt-5a mRNA in unfavorable versus favorable categories in 37 primary NB tumors (P<0.007), we wondered whether retinoic acid (RA), which has a role in neural crest induction and differentiation, might reverse the aberrant negative regulation of Wnt-5a in metastatic malignant neuroblasts. Following treatment with 10 muM RA for 6 days, the MYCN-amplified IGR-N-91 cell lines underwent neuronal differentiation as assessed by reduced MYCN gene expression and neuritic extension. In these conditions, data showed an upregulation of Wnt-5a and PKC-theta; isoform expressions. Our study highlights, for the first time, the involvement of Wnt-5a, which has a role in embryonic and morphogenetic processes, in the response of malignant neuroblasts to RA. In conclusion, we demonstrated that RA, which is used in the treatment of high-risk NB patients with recurrent/residual disease in the bone marrow, is able to upregulate Wnt-5a gene expression.

Cell Differentiation↗

The Bacillus subtilis SinR and RapA developmental regulators are responsible for inhibition of spore development by alcohol.

Even though there is a large body of information concerning the harmful effects of alcohol on different organisms, the mechanism(s) that affects developmental programs, at a single-cell level, has not been clearly identified. In this respect, the spore-forming bacterium Bacillus subtilis constitutes an excellent model to study universal questions of cell fate, cell differentiation, and morphogenesis. Here, we demonstrate that treatment with subinhibitory concentrations of alcohol that did not affect vegetative growth inhibited the initiation of spore development through a selective blockage of key developmental genes under the control of the master transcription factor Spo0A approximately P. Isopropyl-beta-D-thiogalactopyranoside-directed expression of a phosphorylation-independent form of Spo0A (Sad67) and the use of an in vivo mini-Tn10 insertional library permitted the identification of the developmental SinR repressor and RapA phosphatase as the effectors that mediated the inhibitory effect of alcohol on spore morphogenesis. A double rapA sinR mutant strain was completely resistant to the inhibitory effects of different-C-length alcohols on sporulation, indicating that the two cell fate determinants were the main or unique regulators responsible for the spo0 phenotype of wild-type cells in the presence of alcohol. Furthermore, treatment with alcohol produced a significant induction of rapA and sinR, while the stationary-phase induction of sinI, which codes for a SinR inhibitor, was completely turned off by alcohol. As a result, a dramatic repression of spo0A and the genes under its control occurred soon after alcohol addition, inhibiting the onset of sporulation and permitting the evaluation of alternative pathways required for cellular survival.

Bacillus subtilis↗

Clustering of gene hypermethylation associated with clinical risk groups in neuroblastoma.

BACKGROUND: Neuroblastoma is the most common extracranial solid malignancy in infancy and childhood, but the biological factors involved in its development and progression are still unclear. Transcriptional silencing of tumor suppressor genes mediated by hypermethylation of promoter CpG islands is a hallmark of human tumors. We addressed the clinical relevance of promoter hypermethylation in neuroblastoma. METHODS: We examined the methylation status of 45 candidate genes representative of many cellular pathways in 10 neuroblastoma cell lines and of 10 of these genes in 145 tumor samples (118 of them were primary neuroblastomas). We used Fisher's exact test to examine the association of CpG island methylation and clinical subgroups and Kaplan-Meier analysis to determine the association between methylation and survival in primary tumors. Cluster analysis was used to group cell lines and tumors by gene methylation status. Bonferroni-corrected statistical tests were two-sided. RESULTS: Clustering of neuroblastoma cell lines on the basis of hypermethylation distinguished lines with MYCN amplification (a negative prognostic factor) from those without it (P =.012). Promoter hypermethylation of the developmental gene HOXA9 was associated with mortality in noninfant patients (P =.04) and in tumors lacking MYCN amplification (P =.023). Hypermethylation of the proapoptotic gene TMS1 and the cell cycle gene CCND2 was associated with stage 4-progressing tumors (P<.001), but the genes were never methylated in stage 4S tumors, which undergo spontaneous regression. Hypermethylation of the differentiation gene RARbeta2 was associated with patient survival (P =.032). Unsupervised hierarchical cluster analysis of all tumors based on methylation of the 10 genes separated several clinically relevant groups of tumors. CONCLUSIONS: Profiling the status of CpG island hypermethylation in human primary neuroblastomas may have clinicopathologic value.

Cell Line, Tumor↗

Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients.

Split hand foot malformation (SHFM) also known as central ray deficiency, ectrodactyly and cleft hand/foot, is one of the most complex of limb malformations. SHFM can occur as an isolated malformation or in association with other malformations, as in the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and other autosomal dominant conditions with long bone involvement, all showing variable expressivity and reduced penetrance. The deficiency in SHFM patients can also be accompanied by other distal limb anomalies including polydactyly and/or syndactyly. This variability causes the phenotypic classification of SHFM to be far from straightforward and genetic heterogeneity, with at least five loci identified to date, further complicates management of affected patients and their families. Although genotypic-phenotypic correlations have been proposed at the molecular level for SHFM4 patients who have mutations in the P63 gene, phenotypic correlations at the chromosomal level have not been thoroughly documented. Using descriptive epidemiology, Chi square and discriminant function analyses, our laboratory has identified phenotypic patterns associated with the mapped genetic SHFM loci. These findings can assist in classification, provide insight into responsible developmental genes and assist in directing mapping efforts and targeted genetic testing, resulting in more accurate information for family members in the clinical setting. Comparison with relevant animal models is discussed.

Abnormalities, Multiple↗