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Mammalian Development (mammalian + development)
Selected AbstractsGain of function of Tbx1 affects pharyngeal and heart development in the mouseGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 3 2009Francesca Vitelli Abstract Mammalian development is highly sensitive to Tbx1 gene dosage reduction. Gene function insights can also be learned from increased or ectopic expression. The authors generated a novel mouse transgenic line, named COET, which expresses Tbx1 upon Cre-mediated recombination. The authors crossed this transgenic line with Tbx1Cre animals to activate expression in the Tbx1 -expression domain. Compound mutant COET;Tbx1Cre/+ animals died after birth and showed heart enlargement. At E18.5, compound mutants showed ventricular septal defects and thymic abnormalities. The authors crossed compound mutants into a Tbx1 null background to understand whether this phenotype is caused by gene overdosage. Results showed that gene dosage reduction at the endogenous locus could not rescue heart and thymic defects, although the transgene rescued the loss of function phenotype. Thus, the transgenic phenotype appears to be due to gain of function. Resultant data demonstrate that Tbx1 expression must be tightly regulated to be compatible with normal embryonic development. genesis 47:188,195, 2009. © 2009 Wiley-Liss, Inc. [source] Developmental effects of physiologically weak electric fields and heat: An overview,BIOELECTROMAGNETICS, Issue S7 2005Richard D. Saunders Abstract This study summarizes the possible effects on prenatal development of physiologically weak electric fields induced in the body by exposure to extremely low frequency (ELF) electromagnetic fields and of elevated temperature levels that might result from exposure to radiofrequency (RF) radiation. Both topics have been discussed at recent international workshops organized by WHO in collaboration with other bodies. Mammalian development is characterized by a highly ordered sequence of cell proliferation and differentiation, migration, and programmed cell death. These processes, particularly proliferation and migration, are susceptible to a variety of environmental agents including raised maternal temperature. In addition, there is growing evidence that physiologically weak endogenous DC electric fields and ionic currents have a role in guiding developmental processes, including cell orientation and migration, by establishing electrical potential gradients. Disruption of these fields can adversely affect development in amphibian and bird embryos, which are experimentally accessible, and may well do so in mammalian embryos. The extent to which induced ELF electric fields might influence these and other processes that take place during prenatal development, childhood, and adolescence is less clear. Organogenesis, which takes place primarily during the embryonic period, is susceptible to raised maternal temperatures; a large number of studies have shown that RF exposure produces developmental effects that can be attributed to heat. The development of the central nervous system is particularly susceptible to raised temperatures; a reduction in brain size, which results in a smaller head, is one of the most sensitive markers of heat-induced developmental abnormalities and can be correlated with heat-induced behavioral deficits. However, some aspects of CNS development have been less well explored, particularly effects on corticogenesis. In addition, the persistence of CNS developmental sensitivity through to childhood and adolescence is not clear. Bioelectromagnetics Supplement 7:S127,S132, 2005. © 2005 Wiley-Liss, Inc. [source] Epigenetic reprogramming: Enforcer or enabler of developmental fate?DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2010Alexander N. Combes A single fertilized egg is programmed to differentiate into a multitude of distinct cell types that comprise a multicellular organism. Epigenetic mechanisms such as DNA methylation and histone modifications are intricately involved in regulating developmental potential and cellular identity by establishing permissive or repressive chromatin states that are mitotically heritable. Here, we review the dynamics of major epigenetic marks during early mammalian development, and explore the question of whether DNA methylation and chromatin modifications enable or enforce changes that lead to the first cell fate decision. [source] Epigenetic regulation in neural stem cell differentiationDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2010Berry Juliandi The central nervous system (CNS) is composed of three major cell types , neurons, astrocytes, and oligodendrocytes , which differentiate from common multipotent neural stem cells (NSCs). This differentiation process is regulated spatiotemporally during the course of mammalian development. It is becoming apparent that epigenetic regulation is an important cell-intrinsic program, which can interact with transcription factors and environmental cues to modulate the differentiation of NSCs. This knowledge is important given the potential of NSCs to produce specific CNS cell types that will be beneficial for clinical applications. Here we review recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NSC fate during CNS development, with a particular focus on the developing mammalian forebrain. [source] Functional analysis of murine CBF1 during Drosophila developmentDEVELOPMENTAL DYNAMICS, Issue 4 2006Markus Kaspar Abstract Transcription factors of the CSL family are the main mediators of the Notch signalling pathway. The CSL factor in Drosophila is called Suppressor of Hairless (Su(H)) and it has been shown that it acts as a transcriptional repressor in the absence of a Notch signal and as a transcriptional activator in its presence in several developmental contexts. Furthermore, recent data suggest that Su(H) can also activate and maintain transcription of some target genes in a Notch-independent manner. However, although it has been shown that the mammalian CSL ortholog, CBF1, acts as a repressor of transcription in cell culture experiments, so far in vivo evidence for such a function has been lacking. Moreover, it is not known whether CBF1 can activate transcription in a Notch-independent manner, just like Su(H). Here we have investigated these questions by introducing murine CBF1 (mCBF1) and asked whether it can functionally replace Su(H) during Drosophila development. We found that this is indeed the case. We show that mCBF1 can act as a repressor of transcription and can activate and maintain the expression of some target genes in a Notch-independent manner. Our results, therefore, indicate that CBF1 can exert these functions also in its normal context, that is during mammalian development. Developmental Dynamics 235:918,927, 2006. © 2006 Wiley-Liss, Inc. [source] An SNF2 factor involved in mammalian development and cellular proliferationDEVELOPMENTAL DYNAMICS, Issue 1 2001Eric H. Raabe Abstract Members of the SNF2 (Sucrose Non-Fermenter) family of chromatin-remodeling proteins function in processes ranging from DNA repair to transcription to methylation. Using differential display, we recently identified a novel member of the SNF2 family that is highly expressed at the mRNA level in proliferating cells and is down-regulated during apoptosis. We have named this gene PASG (Proliferation-Associated SNF2-like Gene). Northern blot analysis of adult mouse tissues shows PASG to be highly expressed in proliferating organs such as thymus, bone marrow, and testis and absent from nonproliferative tissues such as brain and heart. In situ hybridization analysis of mouse embryos shows that PASG is differentially expressed during development, with highest expression in developing face, limbs, skeletal muscle, heart, and tail. In vitro, PASG expression correlates with a shift from a quiescent to a proliferative state. Mice null for PASG (also known as LSH or Hells) are reported to die perinatally, although the mechanism for lethality is unclear (Geiman and Muegge, 2000). To test the hypothesis that PASG functions in cell proliferation, we compared 5-bromodeoxyuridine (BrdU) incorporation in C33A cells transiently transfected with PASG versus empty vector and found that PASG transfected cells showed a significant decrease in the amount of BrdU incorporation. These findings suggest that PASG plays a role in cell proliferation and may function in the development of multiple cell lineages during murine embryogenesis. © 2001 Wiley-Liss, Inc. [source] Characterization of sequence variations in human histone H1.2 and H1.4 subtypesFEBS JOURNAL, Issue 14 2005Bettina Sarg In humans, eight types of histone H1 exist (H1.1,H1.5, H1°, H1t and H1oo), all consisting of a highly conserved globular domain and less conserved N- and C-terminal tails. Although the precise functions of these isoforms are not yet understood, and H1 subtypes have been found to be dispensable for mammalian development, it is now clear that specific functions may be assigned to certain individual H1 subtypes. Moreover, microsequence variations within the isoforms, such as polymorphisms or mutations, may have biological significance because of the high degree of sequence conservation of these proteins. This study used a hydrophilic interaction liquid chromatographic method to detect sequence variants within the subtypes. Two deviations from wild-type H1 sequences were found. In K562 erythroleukemic cells, alanine at position 17 in H1.2 was replaced by valine, and, in Raji B lymphoblastoid cells, lysine at position 173 in H1.4 was replaced by arginine. We confirmed these findings by DNA sequencing of the corresponding gene segments. In K562 cells, a homozygous GCC,GTC shift was found at codon 18, giving rise to H1.2 Ala17Val because the initial methionine is removed in H1 histones. Raji cells showed a heterozygous AAA,AGA codon change at position 174 in H1.4, corresponding to the Lys173Arg substitution. The allele frequency of these sequence variants in a normal Swedish population was found to be 6.8% for the H1.2 GCC,GTC shift, indicating that this is a relatively frequent polymorphism. The AAA,AGA codon change in H1.4 was detected only in Raji cells and was not present in a normal population or in six other cell lines derived from individuals suffering from Burkitt's lymphoma. The significance of these sequence variants is unclear, but increasing evidence indicates that minor sequence variations in linker histones may change their binding characteristics, influence chromatin remodeling, and specifically affect important cellular functions. [source] Maternal methyl supplements increase offspring DNA methylation at Axin fused,GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 9 2006Robert A. Waterland Abstract Transient environmental exposures during mammalian development can permanently alter gene expression and metabolism by influencing the establishment of epigenetic gene regulatory mechanisms. The genomic characteristics that confer such epigenetic plasticity upon specific loci, however, have not been characterized. Methyl donor supplementation of female mice before and during pregnancy permanently increases DNA methylation at the viable yellow agouti (Avy) metastable epiallele in the offspring. The current study tested whether another murine metastable epiallele, axin fused (AxinFu), similarly exhibits epigenetic plasticity to maternal diet. We found that methyl donor supplementation of female mice before and during pregnancy increased DNA methylation at AxinFu and thereby reduced by half the incidence of tail kinking in AxinFu/+ offspring. The hypermethylation was tail-specific, suggesting a mid-gestation effect. Our results indicate that stochastic establishment of epigenotype at metastable epialleles is, in general, labile to methyl donor nutrition, and such influences are not limited to early embryonic development. genesis 44:401,406, 2006. Published 2006 Wiley-Liss, Inc. [source] The interaction of KCTD1 with transcription factor AP-2, inhibits its transactivation,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2009Xiaofeng Ding Abstract AP-2 is a transcription factor implicated in mammalian development, cell proliferation, apoptosis, and carcinogenesis. To identify potential AP-2,-interacting partners, a yeast two-hybrid screen was performed in human brain cDNA library. One of the identified clones encodes potassium channel tetramerization domain-containing 1 (KCTD1). We demonstrated the novel KCTD1,AP-2, interaction in vitro by GST pull-down assays and in vivo by co-immunoprecipitation assays and mapped the interaction domains to the N-termini of both proteins. In addition, we observed that the two proteins were completely co-localized in the nuclei of mammalian cells. Transient transfection assays using four promoters containing AP-2-binding sites confirmed that KCTD1 significantly repressed AP-2,-mediated transactivation through the BTB domain, whereas KCTD1 siRNA strongly relieved KCTD1-mediated repression of AP-2, transcriptional activity, and other BTB domain proteins such as PDIP1, KCTD10, and TNFAIP1 did not markedly inhibit the transcriptional activity of AP-2,, suggesting that KCTD1 specifically acts as a negative regulator of AP-2,. Finally, we found that KCTD1 interacted with three major members of the AP-2 family and inhibited their transcriptional activities. Taken together, our results indicate the novel function of KCTD1 as the transcriptional repressor for AP-2 family, especially for AP-2,. J. Cell. Biochem. 106: 285,295, 2009. © 2008 Wiley-Liss, Inc. [source] Epigenetic pre-patterning and dynamics during initial stages of mammalian preimplantation developmentJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Theodore P. Rasmussen Mammals, like all multicellular organisms, develop from a single cell,the totipotent zygote. During preimplantation development and subsequent development in utero, over 200 distinct cell types are established and integrated into the organ systems and tissues of the developing organism. Much of the field of mammalian developmental biology is devoted to investigation of mechanisms that govern the formation of complete organs and tissues. In contrast to later development, which consumes the vast majority of time associated with development in utero, preimplantation development and germ layer specification occur rapidly. Yet knowledge is limited regarding the regulatory mechanisms that specify the transient, but pluripotent, cellular lineages that form during the initial stages of mammalian development. Gametogenesis and preimplantation development are marked by dramatic and pervasive epigenetic changes rooted in chromatin dynamics. The fundamental mechanisms that specify subsequent cellular lineages of the conceptus are only now becoming understood, and tend to rely relatively heavily upon broad epigenetic mechanisms in addition to master transcription factors. This review considers epigenetic regulation in the very earliest stages of preimplantation development. In addition, recent advances which indicate that some epigenetic coding is imposed during gametogenesis and maintained during preimplantation development are considered. J. Cell. Physiol. 225: 333,336, 2010. © 2010 Wiley-Liss, Inc. [source] Regulation of the Nanog gene by both positive and negative cis -regulatory elements in embryonal carcinoma cells and embryonic stem cellsMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2009Brian Boer Abstract The transcription factor Nanog is essential for mammalian embryogenesis, as well as the pluripotency of embryonic stem (ES) cells. Work with ES cells and embryonal carcinoma (EC) cells previously identified positive and negative cis -regulatory elements that influence the activity of the Nanog promoter, including adjacent cis -regulatory elements that bind Sox2 and Oct-3/4. Given the importance of Nanog during mammalian development, we examined the cis -regulatory elements required for Nanog promoter activity more closely. In this study, we demonstrate that two positive cis -regulatory elements previously shown to be active in F9 EC cells are also active in ES cells. We also identify a novel negative regulatory region that is located in close proximity to two other positive Nanog cis -regulatory elements. Although this negative regulatory region is active in F9 EC cells and ES cells, it is inactive in P19 EC cells. Furthermore, we demonstrate that one of the positive cis -regulatory elements active in F9 EC cells and ES cells is inactive in P19 EC cells. Together, these and other studies suggest that Nanog transcription is regulated by the interplay of positive and negative cis -regulatory elements. Given that P19 appears to be more closely related to a later developmental stage of mammalian development than F9 and ES cells, differential utilization of cis -regulatory elements may reflect mechanisms used during development to achieve the correct level of Nanog expression as embryogenesis unfolds. Mol. Reprod. Dev. 76: 173,182, 2009. © 2008 Wiley-Liss, Inc. [source] Differential regulation of the Oct-3/4 gene in cell culture model systems that parallel different stages of mammalian developmentMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 8 2008Sunil Kumar Mallanna Abstract Oct-3/4 is an essential transcription factor that regulates stem cell fate during embryogenesis. Previous reports have shown that the Oct-3/4 gene utilizes different enhancers to regulate its expression as development proceeds. However, the cis -elements contributing to the differential activity of these enhancers require further study. Here, we investigated the function of the HMG/POU cassette and LRH-1 site present in the distal enhancer (DE) and the proximal enhancer, respectively. F9 and P19 EC cells were the focus of this study because their differential utilization of Oct-3/4 enhancers parallels the use of these enhancers during different stages of development. We determined that the LRH-1 site functions as a positive and a negative cis -regulatory element in P19 and F9 EC cells, respectively. Furthermore, we determined that the HMG/POU cassette in the DE strongly activates the Oct-3/4 promoter in F9 cells, but is a much weaker positive regulatory element in P19 cells. Given that HMG/POU cassettes play key roles in the regulation of at least seven essential genes, the Oct-3/4 HMG/POU cassette was examined more closely by focusing on Sox2, which can bind to HMG/POU cassettes. Although chromatin immunoprecipitation demonstrated that Sox2 binds to the Oct-3/4 gene equally well in both EC cell lines, tethering Sox2 to the region of the HMG/POU cassette only activated the Oct-3/4 promoter in F9 EC cells. These and other findings suggest that the differential activity of the HMG/POU cassette of the Oct-3/4 gene in EC cells is due to differential action of Sox2 and its associated co-factors. Mol. Reprod. Dev. 75: 1247,1257, 2008. © 2008 Wiley-Liss, Inc. [source] What an epigenome remembersBIOESSAYS, Issue 8 2010Ulrike C. Lange Abstract During mammalian development, maintenance of cell fate through mitotic divisions require faithful replication not only of the DNA but also of a particular epigenetic state. Germline cells have the capacity of erasing this epigenetic memory at crucial times during development, thereby resetting their epigenome. Certain marks, however, appear to escape this reprogramming, which allows their transmission to the offspring and potentially guarantees transgenerational epigenetic inheritance. Here we discuss the molecular requirements for faithful transmission of epigenetic information and our current knowledge about the transmission of epigenetic information through generations. [source] Epithelial branching: The power of self-loathingBIOESSAYS, Issue 3 2007Wen-Chin Lee Branching morphogenesis of epithelia is an important mechanism in mammalian development. The last decade has seen the identification of many signalling pathways and intracellular mechanisms that control epithelial branching. Tissue-level mechanisms that space new branches out have, however, remained an unsolved problem. A recent publication by Nelson et al.1 suggests,if extrapolation from their novel and abstract culture system is valid,that branches may be spaced out by a system of mutual inhibition based on diffusion of TGF,. Such a system would allow a developing tree to arrange itself, without detailed genetic specification, by adaptive self-organization. BioEssays 29: 205,207, 2007. © 2007 Wiley Periodicals, Inc. [source] Three-dimensional culture systems for the expansion of pluripotent embryonic stem cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2010Michael P. Storm Abstract Mouse embryonic stem cell (ESC) lines, and more recently human ESC lines, have become valuable tools for studying early mammalian development. Increasing interest in ESCs and their differentiated progeny in drug discovery and as potential therapeutic agents has highlighted the fact that current two-dimensional (2D) static culturing techniques are inadequate for large-scale production. The culture of mammalian cells in three-dimensional (3D) agitated systems has been shown to overcome many of the restrictions of 2D and is therefore likely to be effective for ESC proliferation. Using murine ESCs as our initial model, we investigated the effectiveness of different 3D culture environments for the expansion of pluripotent ESCs. Solohill Collagen, Solohill FACT, and Cultispher-S microcarriers were employed and used in conjunction with stirred bioreactors. Initial seeding parameters, including cell number and agitation conditions, were found to be critical in promoting attachment to microcarriers and minimizing the size of aggregates formed. While all microcarriers supported the growth of undifferentiated mESCs, Cultispher-S out-performed the Solohill microcarriers. When cultured for successive passages on Cultispher-S microcarriers, mESCs maintained their pluripotency, demonstrated by self-renewal, expression of pluripotency markers and the ability to undergo multi-lineage differentiation. When these optimized conditions were applied to unweaned human ESCs, Cultispher-S microcarriers supported the growth of hESCs that retained expression of pluripotency markers including SSEA4, Tra-1,60, NANOG, and OCT-4. Our study highlights the importance of optimization of initial seeding parameters and provides proof-of-concept data demonstrating the utility of microcarriers and bioreactors for the expansion of hESCs. Biotechnol. Bioeng. 2010;107:683,695. © 2010 Wiley Periodicals, Inc. [source] | ||||||||||||||||||||||