PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Genes, Developmental”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 343 records · Page 19Linked to original sources
PubMedDate not supplied

Finding susceptibility genes for developmental disorders of speech: the long and winding road.

UNLABELLED: Finding susceptibility genes for complex disorders is the next major challenge facing genetics researchers. The purpose of this paper is to stimulate creative thinking about the gene-finding process for developmental speech disorders (DSDs), specifically disorders of articulation/phonology and stuttering. The paper will begin with a review of existing behavioral genetic studies of these phenotypes. This will be followed by a discussion of roadblocks that may impede the molecular study of DSDs, research that is in very early stages of development. As a third objective, the small number of molecular genetic studies of DSDs that have been published or presented will be described. The paper concludes with a discussion of research strategies that may maximize the success of molecular studies of speech phenotypes. It will be argued that progress will most likely be enhanced if theories about biological systems and processes can be used to narrow the search for candidate susceptibility genes. LEARNING OUTCOMES: The reader will be introduced to findings and conceptual issues that relate to the behavioral and molecular genetic investigation of DSDs. After completing this paper, readers should be able to (a) identify key epidemiological findings for the three speech phenotypes that were discussed (DAS, speech delay, and stuttering); (b) summarize the findings of the behavioral genetic studies of speech disorders that were presented; (c) identify four specific challenges that may impede future molecular genetic studies of these phenotypes; (d) describe the methodological sequence that led to the discovery of the FOXP2 gene; and (e) summarize the two research strategies that were presented to potentially reduce sample heterogeneity for future molecular genetics research.

Age of Onset↗
PubMed1990

Upstream elements repress premature expression of an Aspergillus developmental regulatory gene.

The Aspergillus nidulans abaA gene regulates intermediate steps in asexual reproductive development and is itself developmentally regulated. An 822-base-pair DNA fragment from the abaA 5'-flanking region is sufficient to drive developmentally appropriate expression of the Escherichia coli lacZ gene. Deletion analysis showed that this fragment contains elements that repress transcription in vegetative cells and immature conidiophores and that activate transcription later during development. A 45-base-pair region encompassing the major and minor abaA transcription initiation sites contains directly repeated sequences related to the mammalian initiator (Inr) element (S. T. Smale and D. Baltimore, Cell 57:103-113, 1989). This element or sequences in the untranslated leader were sufficient for correct transcription initiation and for measurable developmental induction. Similar elements were present at or near the initiation sites of other developmentally regulated genes. We propose that the temporal and spatial specificity of expression of these genes results from modulation of the activity of Inr elements.

Aspergillus niger↗
PubMed1991

The SGP-2 gene is developmentally regulated in the mouse kidney and abnormally expressed in collecting duct cysts in polycystic kidney disease.

Sulfated glycoprotein-2 (SGP-2) is a secreted, dimeric, glycosylated protein synthesized by a number of different epithelial cell types. Although its function is not yet understood, SGP-2 has been hypothesized to be involved in such diverse processes as the promotion of cell-cell interactions, spermatogenesis, modulation of the complement system, and programmed cell death. We have now found that the SGP-2 gene is developmentally regulated in the mouse kidney. SGP-2 gene expression is first detected in the condensing nephrogenic mesenchyme and is subsequently down-regulated during the maturation of the glomerular epithelia, proximal tubules, and collecting ducts. SGP-2 continues to be expressed in the mature kidney in distal tubules and in the urothelial lining of the calyx and papilla. We have also examined the expression of the SGP-2 gene in polycystic kidneys of the C57BL/6J-cpk mouse, a model of autosomal recessive polycystic kidney disease in which there is development of epithelial-lined cysts arising primarily from the collecting duct system. Abnormally high levels of SGP-2 mRNA were found in the cyst wall epithelium of polycystic kidneys. The expression of the SGP-2 gene in normal development suggests that it plays a role in differentiating epithelial structures; and the abnormally high levels of SGP-2 gene expression in polycystic kidneys suggests that the cells lining cysts are not fully differentiated. It is possible, therefore, that polycystic kidney disease is caused by a defective developmental process in which there is a delay in terminal differentiation.

Animals↗
PubMed1990

Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.

Interferons (IFNs) are a heterogeneous family of cytokines that exhibits multiple biological activities. Upon viral infection, expression of type I IFNs (i.e., IFN-alpha and IFN-beta) is induced in a variety of differentiated cells but not in cells of embryonal origin. IRF-1 and IRF-2, which bind to the same cis-elements within the promoters of type I IFN and IFN-inducible MHC class I genes, were identified previously. Here we demonstrate that the expression of both IRF and IFN genes is developmentally regulated in mouse EC cells; these genes become functional only after cell differentiation. Furthermore, cDNA-directed IRF-1 produced in undifferentiated but not differentiated EC cells efficiently activates the transfected IFN-alpha and IFN-beta and endogenous IFN-alpha genes, whereas IRF-2 represses the IRF-1 effects. These findings emphasize the dual function of the IRF-responsive cis-elements as positive and negative regulators, since they can be occupied by transcriptionally active or inactive IRF molecules. This type of regulatory mechanism might operate in other cytokine systems.

Animals↗
PubMed1998

Cloning of the human interferon-related developmental regulator (IFRD1) gene coding for the PC4 protein, a member of a novel family of developmentally regulated genes.

The rat PC4 gene had been initially isolated as a nerve growth factor-inducible sequence in PC12 cells. Although its function remains unknown, recently it has been shown that PC4 is necessary to muscle differentiation and that it might have a role in signal transduction. We report the isolation of the human homolog of the rat PC4 gene, renamed here IFRD1 (interferon-related developmental regulator 1). Several human IFRD1 clones were identified by searching the EST database using the rat IFRD1 (PC4) cDNA as a query. An EST clone containing the entire ORF was chosen for sequencing. Human IFRD1 presented a predicted protein product of 453 amino acids, highly conserved (90.2% identity) compared to the rat IFRD1 (PC4) protein sequences. The mapping assignment of human IFRD1 to chromosome 7q22-q31 was retrieved from the UniGene database maintained at NCBI. A comparison of human IFRD1 (PC4) protein to databases revealed 47% identity to the protein encoded by the human gene SKMc15, originally isolated from a chromosome 3-specific library. Therefore, SKMc15 is a gene related to IFRD1, being the second member of a novel family. We analyzed their expression during murine development, and we found that mouse IFRD1 appears more expressed in specific differentiating structures at midgestation, while mouse SKMc15 is highly expressed soon after gastrulation and in the hepatic primordium, suggesting an involvement in early hematopoiesis.

Adult↗
PubMed1997

Zis: a developmentally regulated gene expressed in juxtaglomerular cells.

Renal juxtaglomerular (JG) cells are specialized myoepithelioid cells located in the afferent arteriole at the entrance to the glomerulus. Their main function and distinctive feature is the synthesis and release of renin, the key hormone-enzyme of the renin-angiotensin system that regulates arterial blood pressure. Despite their relevance to health and disease, not much is known about factors that confer and/or maintain JG cell identity. To identify genes uniquely expressed in JG cells, we used a cell culture model and RNA differential display. JG cells cultured for 2 days express renin and renin mRNA, but after 10 days in culture they no longer contain or release renin and renin mRNA is reduced 700-fold. We report one cDNA differentially expressed in the 2-day JG cell culture that detects a 2.6-kb mRNA expressed at higher levels in newborn than adult kidney. Screening a 2-day culture JG cell cDNA library yielded clones representing differentially spliced transcripts. These cDNAs encode one unique protein (Zis) containing zinc fingers and domains characteristic of splicing factors and RNA binding proteins. Northern blot analysis confirmed Zis mRNA expression in differentiated JG cells, and identified an additional unique 1.5-kb transcript. The Zis transcripts are developmentally regulated in kidney and a number of other organs. The features of the Zis protein and its organ distribution suggest a possible role in regulation of transcription and/or splicing, both important steps for controlling developmentally expressed genes.

Aging↗
PubMed2003

A genomewide survey of developmentally relevant genes in Ciona intestinalis. II. Genes for homeobox transcription factors.

Homeobox-containing genes play crucial roles in various developmental processes, including body-plan specification, pattern formation and cell-type specification. The present study searched the draft genome sequence and cDNA/EST database of the basal chordate Ciona intestinalis to identify 83 homeobox-containing genes in this animal. This number of homeobox genes in the Ciona genome is smaller than that in the Caenorhabditis elegans, Drosophila melanogaster, human and mouse genomes. Of the 83 genes, 76 have possible human orthologues and 7 may be unique to Ciona. The ascidian homeobox genes were classified into 11 classes, including Hox class, NK class, Paired class, POU class, LIM class, TALE class, SIX class, Prox class, Cut class, ZFH class and HNF1 class, according to the classification scheme devised for known homeobox genes. As to the Hox cluster, the Ciona genome contains single copies of each of the paralogous groups, suggesting that there is a single Hox cluster, if any, but genes orthologous to Hox7, 8, 9 and 11 were not found in the genome. In addition, loss of genes had occurred independently in the Ciona lineage and was noticed in Gbx of the EHGbox subclass, Sax, NK3, Vax and vent of the NK class, Cart, Og9, Anf and Mix of the Paired class, POU-I, III, V and VI of the POU class, Lhx6/7 of the LIM class, TGIF of the TALE class, Cux and SATB of the Cut class, and ZFH1 of the ZFH class, which might have reduced the number of Ciona homeobox genes. Interestingly, one of the newly identified Ciona intestinalis genes and its vertebrate counterparts constitute a novel subclass of HNF1 class homeobox genes. Furthermore, evidence for the gene structures and expression of 54 of the 83 homeobox genes was provided by analysis of ESTs, suggesting that cDNAs for these 54 genes are available. The present data thus reveal the repertoire of homeodomain-containing transcription factors in the Ciona genome, which will be useful for future research on the development and evolution of chordates.

Animals↗
PubMed2003

Selective gene regulation by SWI/SNF-related chromatin remodeling factors.

Chromatin is a highly dynamic structure that plays a key role in the orchestration of gene expression patterns during cellular differentiation and development. The packaging of DNA into chromatin generates a barrier to the transcription machinery. The two main strategies by which cells alleviate chromatin-mediated repression are through the action of ATP-dependent chromatin remodeling complexes and enzymes that covalently modify the histones. Various signaling pathways impinge upon the targeting and activity of these enzymes, thereby controlling gene expression in response to physiological and developmental cues. Chromatin structure also underlies many so-called epigenetic phenomena, leading to the mitotically stable propagation of differential expression of genetic information. Here, we will focus on the role of SWI/SNF-related ATP-dependent chromatin remodeling complexes in developmental gene regulation. First, we compare different models for how remodelers can act in a gene-selective manner, and either cooperate or antagonize other chromatin-modulating systems in the cell. Next, we discuss their functioning during the control of developmental gene expression programs.

Animals↗
PubMed1996

Expression of a developmentally regulated gene, Mng10, in identified neurosecretory cells in the CNS of Manduca sexta.

We are interested in the molecular events underlying the development of the nervous system of Manduca sexta during the final 24 h of the pupal molt. In this article we describe a gene, Mng10, that is expressed in the abdominal nervous system of M. sexta and is developmentally regulated over this 24-h period. In situ hybridization analysis shows that the transcript is localized predominantly to a single pair of uniquely identifiable neurosecretory neurons, the NS-L1 cells in the abdominal ganglia. Mng10 is a single copy gene encoding a 229 amino acid protein with a predicted molecular mass of 26 kDa. At the amino acid level the protein shows 34% identity to the yeast transcription unit, Yer082. Northern blot analysis shows that the transcript of Mng10 is very rare, comprising about 0.001% of the poly (A)+ RNA from the CNS and is detectable at 4 h but not 24 h prior to pupal ecdysis. One of the physiological events that develops over the final 24 h of the pupal molt is the ability of the nervous system to respond to the neuropeptide eclosion hormone. In this context, it is interesting to note that the NS-L1 cells are members of the group of 50 neurons that show increased cGMP immunoreactivity when the nervous system is exposed to the neuropeptide eclosion hormone.

Amino Acid Sequence↗
PubMed1992

Pax1, a member of the paired box-containing class of developmental control genes, is mapped to human chromosome 20p11.2 by in situ hybridization (ISH and FISH).

Pax-1, a member of a murine multigene family, belongs to the paired box-containing class of developmental control genes first identified in Drosophila. The Pax-1 gene encodes a sequence-specific DNA-binding protein with transcriptional activating properties and has been found to be mutated in the autosomal recessive mutation undulated (un) on mouse chromosome 2 with vertebral anomalies along the entire rostrocaudal axis. By radioactive in situ hybridization (ISH) using a fragment from the murine Pax-1 paired box that is almost identical to the respective sequences from the cognate human gene HuP48 and fluorescence in situ hybridization (FISH) using a complete mouse Pax-1 cDNA, we have assigned the human homologue of murine Pax-1, the PAX1 locus, to chromosome 20p. The map position of PAX1 after FISH (FL-pter value of 0.34 +/- 0.04) corresponds to band p11.2. These results confirm the exceptional homology between human chromosome 20 and the distal segment of mouse chromosome 2, extending from bands F to G, and add PAX1 to the group of genes on 20p like PTPA, PRNP, SCG1, BMP2A, which are located in proximity on both chromosomes.

Animals↗
PubMed1993

Deficient testicular and adrenal steroidogenesis in mutant cream (e/e) Syrian hamsters.

Coat color genes have been shown to be developmental genes with wide pleiotropic actions. The present study was undertaken to analyze the effects of mutations at the e locus of the Syrian hamster on testicular and adrenal steroidogenesis. Although no differences in body weight were detected, cream (e/e) hamsters had larger testes and smaller adrenals than wildtype (+/+) animals. Plasma testosterone levels were lower in e/e than in +/+ hamsters. However; testicular progesterone levels were higher, and 17-OH-progesterone and testosterone levels were lower in e/e when compared to +/+ hamsters. The efficiency of testicular 17-hydroxylase appear to be reduced in e/e hamsters. Adrenal progesterone levels were higher. 17-OH-progesterone, testosterone, dehydroepiandrosterone sulphate and aldosterone levels were similar, and cortisol levels were lower in e/e when compared to +/+ hamsters. The efficiencies of adrenal 17-hydroxylase and 17-hydroxysteroid dehydrogenase appear to be reduced in e/e hamsters. The present data indicate that steroidogenic deficiencies are present in the testes and adrenals of e/e hamsters, and that the gonadal alterations are more severe than the adrenal ones. The e locus, in the hamster, could be a developmental gene, or could be coding for a component in a signaling pathway under the control of such a gene.

Adrenal Cortex↗
PubMed2006

Distinct sets of developmentally regulated genes that are expressed by human oocytes and human embryonic stem cells.

OBJECTIVE: To identify genes that are expressed differently during final oocyte maturation and early embryonic development in humans. DESIGN: Comparison of gene expression profiles of human germinal vesicle oocytes (hGVO), human embryonic stem cells (hESC) and human foreskin fibroblasts. SETTING: Research centers and a fertility unit in a university hospital. PATIENT(S): Fifty-five healthy women donated 76 hGVO. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gene expression profiles were analyzed and compared with the use of microarray and reverse-transcription polymerase chain reaction. RESULT(S): Altogether, 10,183 genes were expressed in hGVO, and 45% of these genes were unclassified by biologic function. Four oocyte-specific genes (MATER, ZAR1, NPM2 and FIGLA) were detected in hGVO for the first time. Known components of 4 signaling pathways (MOS-MPF, transforming growth factor-beta, WNT, and NOTCH) were also found expressed in hGVO, with some components detected in hGVO for the first time. Distinct sets of genes that were revealed by comparison of expression profiles between hGVO, hESC, and human foreskin fibroblasts appear to be involved in oocyte maturation and early embryonic development. CONCLUSION(S): We obtained, for the first time, a large amount of information on gene expression of hGVO as compared with hESC. These data, from a unique research material-human oocytes, can now be used to understand the molecular mechanisms of early human development.

Adult↗
PubMed2000

Developmentally regulated gene expression of Th2 cytokines in the brain.

Given the critical role of cytokines in the regulation of an inflammatory response, we investigated whether certain cytokines are expressed in the brains of normal mice during maturation that could contribute to the immune-privileged nature of the CNS or potentially influence an immune-mediated illness such as experimental allergic encephalomyelitis. The gene expression of IFN gamma (Th1 cytokine) and IL-4 (Th2 cytokine) was analyzed in the brain of several strains of mice. IFN gamma was not detectable. However, IL-4 was present in the brains of neonatal mice, but not adult mice. Resident CNS cells are believed to be the source of the IL-4, because mice deficient in T cells (SCID and RAG2-/-) expressed the IL-4 gene in the CNS. Further analysis indicated that the gene expression of the Th2 cytokine transcription factor, GATA-3, correlated with IL-4 and IL-10 expression in the brain. Since GATA-3-deficient mice have an abnormal CNS, brain-derived Th2 cytokines may play an important role in CNS development, as well as potentially contribute to the immune-privileged nature of the brain.

Age Factors↗
PubMed2000

Identification of the novel developmentally regulated gene, Bdm2, which is highly expressed in fetal rat brain.

Most of the neurogenesis take place during the embryonic stage; the genes expressed predominantly in this stage may play important roles in the control of development of the central nervous system. Using a differential display method, we identified the novel rat gene, brain development-related molecule 2 (Bdm2), that is expressed more abundantly in the embryonic brain than in the adult brain. Full-length Bdm2 cDNA consists of 1842 base pairs (bp) and contains an open reading frame of 1260 bp. Northern blot analysis demonstrated that Bdm2 was strongly expressed in the late embryonic brain and was still detected at lower levels in an early postnatal period; in adults, Bdm2 mRNA was decreased to an undetectable level in brain, though the expression of this mRNA was revealed in other tissues. Level of Bdm2 mRNA was maintained during neuronal differentiation of mouse embryonal carcinoma cell P19, but decreased during the differentiation to glial and unidentified non-neuronal cells. In situ hybridization study demonstrated the wide distribution of Bdm2 mRNA in the embryonic brain; in the adult brain, the hybridization signals became more restricted to the hippocampus, olfactory bulb, cerebellum, and neocortex, almost coinciding with the regions where nascent and immature neurons are present. Thus, it appears likely that Bdm2 encodes a protein that is involved in both the regulation of growth of undifferentiated neural cells and the terminal differentiation of neuronal cells.

Amino Acid Sequence↗
PubMed1999

Molecular cloning and characterization of a novel developmentally regulated gene, Bdm1, showing predominant expression in postnatal rat brain.

Postnatal development, such as synapse refinement, is necessary for the establishment of a mature and functional central nervous system (CNS). Using differential display analysis, we identified a novel gene, termed Bdm1, that is more abundantly expressed in the adult brain than in the embryonic brain. The full-length Bdm1 cDNA is 2718 base pairs long and contains an open reading frame of 1059 base pairs encoding a 38-kDa protein. Northern blot analysis revealed that expression of Bdm1 mRNA in the brain was weak on embryonic days and increased in the early postnatal period. Bdm1 mRNA was significantly expressed in the brain and heart, but there was no or little expression in other tissues. During the differentiation of mouse carcinoma cells P19 to neuron-like cells by retinoic acid, Bdm1 mRNA was up-regulated almost parallel to neurofilament mRNA. Expression of Bdm1 mRNA was observed appreciably in PC12 cells after neuronal differentiation but not in the nonneural cell lines examined. In situ hybridization demonstrated that Bdm1 was expressed widely in the olfactory bulb, cerebral cortex, hippocampus, cerebellum, thalamus, and medulla oblongata. Taken together, these data suggest that Bdm1 gene plays a role in the early postnatal development and function of neuronal cells.

Amino Acid Sequence↗
PubMed1992

Stage-specific expression of a developmentally regulated gene in Dirofilaria immitis.

A previously reported cDNA clone encoding 34 kDa antigenic polypeptide of Dirofilaria immitis (lambda cD34) was studied to elucidate the mechanism of stage-specific gene expression. The 34 kDa polypeptide was a larva-specific antigen and the mRNA was detectable in microfilariae but not in adult worms and eggs. The lambda cD34 gene was not sex linked and was contained in the genome of D. immitis at each stage. The stage-specific expression of the developmentally regulated gene in D. immitis may be controlled primarily at the mRNA level.

Animals↗