The nuclear lamina in adult mammalian somatic cells is composed of three major proteins, lamins A, B, and C. The expression of these proteins during the differentiation of teratocarcinomas and mouse embryogenesis is described. Embryos up to day 8 of gestation and embryonal carcinoma (EC) cells express only a single lamin species closely resembling, if not identical to, lamin B. Lamins A and/or C were detected in fertilized eggs, but disappear during the first 2-4 cleavage divisions, only reappearing in 8 day post-implantation embryos. These two lamins are absent from EC cells, but are strongly expressed in some of their derivatives. These results show that cells of the early mouse embryo do not have a functional requirement for lamins A and C and imply that the structural organization of the nucleus may change fundamentally during embryogenesis.
"Immunofluorescence staining and immunoblotting with isotype specific anti-Lamin antibodies in mouse embryos show low expression of Lamin A/C in ESCs, which increases as cells differentiate (Constantinescu et al., 2006; Eckersley-Maslin et al., 2013). In mice, the increase in Lamin A/C expression is initiated as early as embryonic day 9 and as late as in the adult animal depending on the tissue type (Stewart and Burke, 1987; Rober et al., 1989). In direct support of a role for Lamin A in cell differentiation, experiments in mouse cells testing the effect of Lamin A levels on somatic to iPS cell reprogramming show that depletion of Lamin A accelerates the transition to pluripotency, while cells overexpressing Lamin A take longer to reprogram (Zuo et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: The eukaryotic cell nucleus houses an organism's genome and is the location within the cell where all signaling induced and development-driven gene expression programs are ultimately specified. The genome is enclosed and separated from the cytoplasm by the nuclear envelope (NE), a double-lipid membrane bilayer, which contains a large variety of trans-membrane and associated protein complexes. In recent years, research regarding multiple aspects of the cell nucleus points to a highly dynamic and coordinated concert of efforts between chromatin and the NE in regulation of gene expression. Details of how this concert is orchestrated and how it directs cell differentiation and disease are coming to light at a rapid pace. Here we review existing and emerging concepts of how interactions between the genome and the NE may contribute to tissue specific gene expression programs to determine cell fate.
Frontiers in Genetics 03/2015; 6:95. DOI:10.3389/fgene.2015.00095
"During mouse embryonic development, expression of Lamin A/C is first detected on day 9 in extraembryonic tissues and on day 12 in the embryo itself (Rober et al., 1989). Embryonic carcinoma cells generally express little or no Lamin A/C (Stewart and Burke, 1987; Prather et al., 1989). Lastly, certain adult cell types that are not fully differentiated also express little or no Lamin A/C (Lourim and Lin, 1989; Rober et al., 1989). "
[Show abstract][Hide abstract] ABSTRACT: Lamin A/C is a structural protein of the nuclear envelope and cardiac involvement in Lamin A/C mutations was one of the first phenotypes to be reported in humans, suggesting a crucial role of this protein in the cardiomyocytes function. Mutations in LMNA gene cause a class of pathologies generically named ‘Lamanopathies’ mainly involving heart and skeletal muscles. Moreover, the well known disease called Hutchinson-Gilford Progeria Syndrome (HGPS) due to extensive mutations in LMNA gene, in addition to the systemic phenotype of premature aging, is characterized by the death of patients at around 13 typically for a heart attack or stroke, suggesting again the heart as the main site sensitive to Lamin A/C disfunction. Indeed, the identification of the roles of the Lamin A/C in cardiomyocytes function is a key area of exploration.One of the primary biological roles recently conferred to Lamin A/C is to affect contractile cells lineage determination and senescence. Then, in differentiated adult cardiomyocytes both the ‘structural’ and ‘gene expression hypothesis’ could explain the role of Lamin A in the function of cardiomyocytes. In fact, recent advances in the field propose that the structural weakness/stiffness of the NE, regulated by Lamin A/C amount in NE, can ‘consequently’ alter gene expression.This article is protected by copyright. All rights reserved
Biology of the Cell 07/2014; 106(10). DOI:10.1111/boc.201400033 · 3.51 Impact Factor
"There are three lamin genes in mammalian cells (LMNA, LMNB1, and LMNB2) that encode the A-and B-type lamins. At least one B-type lamin protein is thought to be expressed in all nucleated, metazoan cell types, but the A-type lamins, lamin A and C produced from alternative splicing of LMNA, are developmentally regulated  . It was generally accepted that A-type lamins are not expressed in embryonic stem cells (ESCs) , but a recent study has detected low levels of expression at both the mRNA and protein level in murine ESCs , suggesting that there may be fundamental differences between mouse and human, and raising questions about the effect of expression level on lamin A/C function. "
[Show abstract][Hide abstract] ABSTRACT: The spatial organization of the nucleus results in a compartmentalized structure that affects all aspects of nuclear function. This compartmentalization involves genome organization as well as the formation of nuclear bodies and plays a role in many functions, including gene regulation, genome stability, replication, and RNA processing. Here we review the recent findings associated with the spatial organization of the nucleus and reveal that a common theme for nuclear proteins is their ability to participate in a variety of functions and pathways. We consider this multiplicity of function in terms of Crowdsourcing, a recent phenomenon in the world of information technology, and suggest that this model provides a novel way to synthesize the many intersections between nuclear organization and function.
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