Precision in Practice: The Critical Role of Mesh and Procedure Type Specification in Urogynecological Surgeries and Research.

Recently, the debate surrounding the use of mesh in urogynecological procedures has intensified, leading to FDA warnings and heightened safety concerns. This clinical opinion emphasizes the vital need to specify mesh types in these procedures, drawing attention to the risk profiles and clinical outcomes associated with various meshes and the procedures that utilize them. A significant issue identified in contemporary literature is the tendency to group diverse mesh types under the same umbrella, disregarding their unique characteristics and applications. We describe the range of mesh types, their application routes, and associated complications, highlighting the risks of this nonspecific approach to patient safety and informed decision making. We critically examine the generalization of mesh terminology in clinical and research dialogues. Concluding with specific recommendations for health care providers and researchers, the paper advocates for a more nuanced understanding and communication in the field, ultimately aiming to improve patient care and safety in urogynecological practice.

Slitrk4 is required for the development of inhibitory neurons in the fear memory circuit of the lateral amygdala.

The Slitrk family consists of six synaptic adhesion molecules, some of which are associated with neuropsychiatric disorders. In this study, we aimed to investigate the physiological role of Slitrk4 by analyzing Slitrk4 knockout (KO) mice. The Slitrk4 protein was widely detected in the brain and was abundant in the olfactory bulb and amygdala. In a systematic behavioral analysis, male Slitrk4 KO mice exhibited an enhanced fear memory acquisition in a cued test for classical fear conditioning, and social behavior deficits in reciprocal social interaction tests. In an electrophysiological analysis using amygdala slices, Slitrk4 KO mice showed enhanced long-term potentiation in the thalamo-amygdala afferents and reduced feedback inhibition. In the molecular marker analysis of Slitrk4 KO brains, the number of calretinin (CR)-positive interneurons was decreased in the anterior part of the lateral amygdala nuclei at the adult stage. In in vitro experiments for neuronal differentiation, Slitrk4-deficient embryonic stem cells were defective in inducing GABAergic interneurons with an altered response to sonic hedgehog signaling activation that was involved in the generation of GABAergic interneuron subsets. These results indicate that Slitrk4 function is related to the development of inhibitory neurons in the fear memory circuit and would contribute to a better understanding of osttraumatic stress disorder, in which an altered expression of Slitrk4 has been reported.

Fluorescence In Situ Hybridization as a Tool for Studying the Specification and Differentiation of Cell Types in Nematostella vectensis.

The sea anemone Nematostella vectensis is a genetically tractable cnidarian species that has become a model organism for studying the evolution of developmental processes and genome regulation, resilience to fluctuations in environmental conditions, and the response to pollutants. Gene expression analyses are central to many of these studies, and in situ hybridization has been an important method for obtaining spatial information, in particular during embryonic development. Like other cnidarians, Nematostella embryos are of comparably low morphological complexity, but they possess many cell types that are dispersed throughout the tissue and originate from broad and overlapping areas. These features have made two-color fluorescence in situ hybridization an important method to determine potential co-expression of genes and to generate hypotheses for their functions in cell fate specification. We here share protocols for single and double fluorescence in situ hybridization in Nematostella and for the combination of fluorescence in situ hybridization and immunofluorescence.

Graded FGF activity patterns distinct cell types within the apical sensory organ of the sea anemone Nematostella vectensis.

Bilaterian animals have evolved complex sensory organs comprised of distinct cell types that function coordinately to sense the environment. Each sensory unit has a defined architecture built from component cell types, including sensory cells, non-sensory support cells, and dedicated sensory neurons. Whether this characteristic cellular composition is present in the sensory organs of non-bilaterian animals is unknown. Here, we interrogate the cell type composition and gene regulatory networks controlling development of the larval apical sensory organ in the sea anemone Nematostella vectensis. Using single cell RNA sequencing and imaging approaches, we reveal two unique cell types in the Nematostella apical sensory organ, GABAergic sensory cells and a putative non-sensory support cell population. Further, we identify the paired-like (PRD) homeodomain gene prd146 as a specific sensory cell marker and show that Prd146+ sensory cells become post-mitotic after gastrulation. Genetic loss of function approaches show that Prd146 is essential for apical sensory organ development. Using a candidate gene knockdown approach, we place prd146 downstream of FGF signaling in the apical sensory organ gene regulatory network. Further, we demonstrate that an aboral FGF activity gradient coordinately regulates the specification of both sensory and support cells. Collectively, these experiments define the genetic basis for apical sensory organ development in a non-bilaterian animal and reveal an unanticipated degree of complexity in a prototypic sensory structure.

Single-cell transcriptomics identifies conserved regulators of neuroglandular lineages.

Communication in bilaterian nervous systems is mediated by electrical and secreted signals; however, the evolutionary origin and relation of neurons to other secretory cell types has not been elucidated. Here, we use developmental single-cell RNA sequencing in the cnidarian Nematostella vectensis, representing an early evolutionary lineage with a simple nervous system. Validated by transgenics, we demonstrate that neurons, stinging cells, and gland cells arise from a common multipotent progenitor population. We identify the conserved transcription factor gene SoxC as a key upstream regulator of all neuroglandular lineages and demonstrate that SoxC knockdown eliminates both neuronal and secretory cell types. While in vertebrates and many other bilaterians neurogenesis is largely restricted to early developmental stages, we show that in the sea anemone, differentiation of neuroglandular cells is maintained throughout all life stages, and follows the same molecular trajectories from embryo to adulthood, ensuring lifelong homeostasis of neuroglandular cell lineages.

Pum2 and TDP-43 refine area-specific cytoarchitecture post-mitotically and modulate translation of Sox5, Bcl11b, and Rorb mRNAs in developing mouse neocortex.

In the neocortex, functionally distinct areas process specific types of information. Area identity is established by morphogens and transcriptional master regulators, but downstream mechanisms driving area-specific neuronal specification remain unclear. Here, we reveal a role for RNA-binding proteins in defining area-specific cytoarchitecture. Mice lacking Pum2 or overexpressing human TDP-43 show apparent 'motorization' of layers IV and V of primary somatosensory cortex (S1), characterized by dramatic expansion of cells co-expressing Sox5 and Bcl11b/Ctip2, a hallmark of subcerebral projection neurons, at the expense of cells expressing the layer IV neuronal marker Rorß. Moreover, retrograde labeling experiments with cholera toxin B in Pum2; Emx1-Cre and TDP43A315T mice revealed a corresponding increase in subcerebral connectivity of these neurons in S1. Intriguingly, other key features of somatosensory area identity are largely preserved, suggesting that Pum2 and TDP-43 may function in a downstream program, rather than controlling area identity per se. Transfection of primary neurons and in utero electroporation (IUE) suggest cell-autonomous and post-mitotic modulation of Sox5, Bcl11b/Ctip2, and Rorß levels. Mechanistically, we find that Pum2 and TDP-43 directly interact with and affect the translation of mRNAs encoding Sox5, Bcl11b/Ctip2, and Rorß. In contrast, effects on the levels of these mRNAs were not detectable in qRT-PCR or single-molecule fluorescent in situ hybridization assays, and we also did not detect effects on their splicing or polyadenylation patterns. Our results support the notion that post-transcriptional regulatory programs involving translational regulation and mediated by Pum2 and TDP-43 contribute to elaboration of area-specific neuronal identity and connectivity in the neocortex.

Neuronal identities derived by misexpression of the POU IV sensory determinant in a protovertebrate.

The protovertebrate Ciona intestinalis type A (sometimes called Ciona robusta) contains a series of sensory cell types distributed across the head-tail axis of swimming tadpoles. They arise from lateral regions of the neural plate that exhibit properties of vertebrate placodes and neural crest. The sensory determinant POU IV/Brn3 is known to work in concert with regional determinants, such as Foxg and Neurogenin, to produce palp sensory cells (PSCs) and bipolar tail neurons (BTNs), in head and tail regions, respectively. A combination of single-cell RNA-sequencing (scRNA-seq) assays, computational analysis, and experimental manipulations suggests that misexpression of POU IV results in variable transformations of epidermal cells into hybrid sensory cell types, including those exhibiting properties of both PSCs and BTNs. Hybrid properties are due to coexpression of Foxg and Neurogenin that is triggered by an unexpected POU IV feedback loop. Hybrid cells were also found to express a synthetic gene battery that is not coexpressed in any known cell type. We discuss these results with respect to the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants.

Identification of long noncoding RNAs in injury-resilient and injury-susceptible mouse retinal ganglion cells.

BACKGROUND: Emerging evidence indicates that long noncoding RNAs (lncRNAs) are important regulators of various biological processes, and their expression can be altered following certain pathological conditions, including central nervous system injury. Retinal ganglion cells (RGCs), whose axons form the optic nerve, are a heterogeneous population of neurons with more than 40 molecularly distinct subtypes in mouse. While most RGCs, including the ON-OFF direction-selective RGCs (ooDSGCs), are vulnerable to axonal injury, a small population of RGCs, including the intrinsically photosensitive RGCs (ipRGCs), are more resilient. RESULTS: By performing systematic analyses on RNA-sequencing data, here we identify lncRNAs that are expressed in ooDSGCs and ipRGCs with and without axonal injury. Our results reveal a repertoire of different classes of lncRNAs, including long intergenic noncoding RNAs and antisense ncRNAs that are differentially expressed between these RGC types. Strikingly, we also found dozens of lncRNAs whose expressions are altered markedly in response to axonal injury, some of which are expressed exclusively in either one of the types. Moreover, analyses into these lncRNAs unraveled their neighboring coding genes, many of which encode transcription factors and signaling molecules, suggesting that these lncRNAs may act in cis to regulate important biological processes in these neurons. Lastly, guilt-by-association analysis showed that lncRNAs are correlated with apoptosis associated genes, suggesting potential roles for these lncRNAs in RGC survival. CONCLUSIONS: Overall, the results of this study reveal RGC type-specific expression of lncRNAs and provide a foundation for future investigation of the function of lncRNAs in regulating neuronal type specification and survival.

Genetic interplay between transcription factor Pou4f1/Brn3a and neurotrophin receptor Ret in retinal ganglion cell type specification.

BACKGROUND: While the transcriptional code governing retinal ganglion cell (RGC) type specification begins to be understood, its interplay with neurotrophic signaling is largely unexplored. In mice, the transcription factor Brn3a/Pou4f1 is expressed in most RGCs, and is required for the specification of RGCs with small dendritic arbors. The Glial Derived Neurotrophic Factor (GDNF) receptor Ret is expressed in a subset of RGCs, including some expressing Brn3a, but its role in RGC development is not defined. METHODS: Here we use combinatorial genetic experiments using conditional knock-in reporter alleles at the Brn3a and Ret loci, in combination with retina- or Ret specific Cre drivers, to generate complete or mosaic genetic ablations of either Brn3a or Ret in RGCs. We then use sparse labelling to investigate Brn3a and Ret gene dosage effects on RGC dendritic arbor morphology. In addition, we use immunostaining and/or gene expression profiling by RNASeq to identify transcriptional targets relevant for the potential Brn3a-Ret interaction in RGC development. RESULTS: We find that mosaic gene dosage manipulation of the transcription factor Brn3a/Pou4f1 in neurotrophic receptor Ret heterozygote RGCs results in altered cell fate decisions and/or morphological dendritic defects. Specific RGC types are lost if Brn3a is ablated during embryogenesis and only mildly affected by postnatal Brn3a ablation. Sparse but not complete Brn3a heterozygosity combined with complete Ret heterozygosity has striking effects on RGC type distribution. Brn3a only mildly modulates Ret transcription, while Ret knockouts exhibit slightly skewed Brn3a and Brn3b expression during development that is corrected by adult age. Brn3a loss of function modestly but significantly affects distribution of Ret co-receptors GFRα1-3, and neurotrophin receptors TrkA and TrkC in RGCs. CONCLUSIONS: Based on these observations, we propose that Brn3a and Ret converge onto developmental pathways that control RGC type specification, potentially through a competitive mechanism requiring signaling from the surrounding tissue.

Specific chromatin changes mark lateral organ founder cells in the Arabidopsis inflorescence meristem.

Fluorescence-activated cell sorting (FACS) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were combined to analyse the chromatin state of lateral organ founder cells (LOFCs) in the peripheral zone of the Arabidopsis apetala1-1 cauliflower-1 double mutant inflorescence meristem. On a genome-wide level, we observed a striking correlation between transposase hypersensitive sites (THSs) detected by ATAC-seq and DNase I hypersensitive sites (DHSs). The mostly expanded DHSs were often substructured into several individual THSs, which correlated with phylogenetically conserved DNA sequences or enhancer elements. Comparing chromatin accessibility with available RNA-seq data, THS change configuration was reflected by gene activation or repression and chromatin regions acquired or lost transposase accessibility in direct correlation with gene expression levels in LOFCs. This was most pronounced immediately upstream of the transcription start, where genome-wide THSs were abundant in a complementary pattern to established H3K4me3 activation or H3K27me3 repression marks. At this resolution, the combined application of FACS/ATAC-seq is widely applicable to detect chromatin changes during cell-type specification and facilitates the detection of regulatory elements in plant promoters.

High temperature limits on developmental canalization in the ascidian Ciona intestinalis.

The normal embryogenesis of marine animals is typically confined to a species-specific range of temperatures. Within that temperature range development results in a consistent, or canalized, phenotype, whereas above and below the range abnormal phenotypes are produced. This study reveals a high temperature threshold, occurring over a 1-2 °C range, for normal embryonic development in C. intestinalis. Above that threshold the prevalence of morphological abnormalities increases significantly, beginning with cleavage and gastrula stages, and becoming more pronounced as embryogenesis proceeds. However, even in highly morphologically abnormal temperature disrupted (TD) embryos, muscle, endoderm, notochord, epidermis, and sensory pigment cells are recognizable, as evidenced by histochemical markers or morphology. On the other hand, morphogenesis of the notochord and other structures is dependent on precise cell movement and shape changes after the gastrula stage, which are disrupted above the high temperature threshold. These findings suggest that morphogenetic processes may be more sensitive to high temperature than cell type specification events. They also point to avenues for investigation of the limiting factors to developmental canalization in marine invertebrates.

Precision in the development of neocortical architecture: From progenitors to cortical networks.

Of all brain regions, the 6-layered neocortex has undergone the most dramatic changes in size and complexity during mammalian brain evolution. These changes, occurring in the context of a conserved set of organizational features that emerge through stereotypical developmental processes, are considered responsible for the cognitive capacities and sensory specializations represented within the mammalian clade. The modern experimental era of developmental neurobiology, spanning 6 decades, has deciphered a number of mechanisms responsible for producing the diversity of cortical neuron types, their precise connectivity and the role of gene by environment interactions. Here, experiments providing insight into the development of cortical projection neuron differentiation and connectivity are reviewed. This current perspective integrates discussion of classic studies and new findings, based on recent technical advances, to highlight an improved understanding of the neuronal complexity and precise connectivity of cortical circuitry. These descriptive advances bring new opportunities for studies related to the developmental origins of cortical circuits that will, in turn, improve the prospects of identifying pathogenic targets of neurodevelopmental disorders.

Pias3 is necessary for dorso-ventral patterning and visual response of retinal cones but is not required for rod photoreceptor differentiation.

Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding specification of rod and cone photoreceptors through post-translational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted in complete loss of the Pias3 protein. Pias3-/- mice did not show any overt phenotype, and retinal lamination appeared normal even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography following green light stimulation of postnatal day (P)21 Pias3-/- retina, suggesting a compromised visual response of medium wavelength (M) cones. No change was evident in response of short wavelength (S) cones or rod photoreceptors until 7 months. Increased S-opsin expression in the M-cone dominant dorsal retina suggested altered distribution of cone photoreceptors. Transcriptome profiling of P21 and 18-month-old Pias3-/- retina revealed aberrant expression of a subset of photoreceptor genes. Our studies demonstrate functional redundancy in SUMOylation-associated transcriptional control mechanisms and identify a specific, though limited, role of Pias3 in modulating spatial patterning and optimal function of cone photoreceptor subtypes in the mouse retina.

FoxO1: a novel insight into its molecular mechanisms in the regulation of skeletal muscle differentiation and fiber type specification.

FoxO1, a member of the forkhead transcription factor forkhead box protein O (FoxO) family, is predominantly expressed in most muscle types. FoxO1 is a key regulator of muscle growth, metabolism, cell proliferation and differentiation. In the past two decades, many researches have indicated that FoxO1 is a negative regulator of skeletal muscle differentiation while contrasting opinions consider that FoxO1 is crucial for myoblast fusion. FoxO1 is expressed much higher in fast twitch fiber enriched muscles than in slow muscles and is also closely related to muscle fiber type specification. In this review, we summarize the molecular mechanisms of FoxO1 in the regulation of skeletal muscle differentiation and fiber type specification.

Restricting calcium currents is required for correct fiber type specification in skeletal muscle.

Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease.

Evolutionary reconstruction of pattern formation in 98 Dictyostelium species reveals that cell-type specialization by lateral inhibition is a derived trait.

BACKGROUND: Multicellularity provides organisms with opportunities for cell-type specialization, but requires novel mechanisms to position correct proportions of different cell types throughout the organism. Dictyostelid social amoebas display an early form of multicellularity, where amoebas aggregate to form fruiting bodies, which contain only spores or up to four additional cell-types. These cell types will form the stalk and support structures for the stalk and spore head. Phylogenetic inference subdivides Dictyostelia into four major groups, with the model organism D. discoideum residing in group 4. In D. discoideum differentiation of its five cell types is dominated by lateral inhibition-type mechanisms that trigger scattered cell differentiation, with tissue patterns being formed by cell sorting. RESULTS: To reconstruct the evolution of pattern formation in Dictyostelia, we used cell-type specific antibodies and promoter-reporter fusion constructs to investigate pattern formation in 98 species that represent all groupings. Our results indicate that in all early diverging Dictyostelia and most members of groups 1-3, cells differentiate into maximally two cell types, prestalk and prespore cells, with pattern formation being dominated by position-dependent transdifferentiation of prespore cells into prestalk cells. In clade 2A, prestalk and stalk cell differentiation are lost and the prespore cells construct an acellular stalk. Group 4 species set aside correct proportions of prestalk and prespore cells early in development, and differentiate into up to three more supporting cell types. CONCLUSIONS: Our experiments show that positional transdifferentiation is the ancestral mode of pattern formation in Dictyostelia. The early specification of a prestalk population equal to the number of stalk cells is a derived trait that emerged in group 4 and a few late diverging species in the other groups. Group 4 spore masses are larger than those of other groups and the differentiation of supporting cell types by lateral inhibition may have facilitated this increase in size. The signal DIF-1, which is secreted by prespore cells, triggers differentiation of supporting cell types. The synthesis and degradation of DIF-1 were shown to be restricted to group 4. This suggests that the emergence of DIF-1 signalling caused increased cell-type specialization in this group.

Virus del papiloma humano (VPH) detección y tipificación en la consulta privada / Human papilloma virus (HPV) detection and typification in private practice

Determinar cuáles son los tipos de virus del papiloma humano en mujeres y hombres que asisten a una consulta privada de ginecología. Se estudiaron 200 pacientes: 175 mujeres y 25 hombres, con diagnóstico de virus del papiloma humano a simple vista, colposcopia, citología y/o biopsia. A todos se les realizó tipificación de virus del papiloma humano por reacción en cadena de la polimerasa. En la Unidad de Ginecología Reproducción y Salud Integral. Valencia. La edad de los pacientes se ubicó en más del 70 por ciento en los grupos etarios de 15 a 34 años. Las pacientes nuligestas y nulíparas estaban alrededor del 60 por ciento. La imagen colposcópica dominante en las mujeres fue epitelio aceto-blanco (77 por ciento), mientras que en la totalidad de los hombres correspondió a verrugas. La citología cervical reportó virus del papiloma humano (con o sin NIC) en solo 40 por ciento, mientras que la biopsia lo demostró cerca del 80 por ciento. Se realizó detección/tipificación de virus del papiloma humano por el método de reacción en cadena de la polimerasa en todos los casos, encontrándose cerca del 10 por ciento de resultados negativos en mujeres y 12 por ciento en hombres. Fueron hallados 15 tipos de virus del papiloma humano en mujeres, de los cuales más de la mitad eran de alto riesgo. En los hombres solo encontramos 5 tipos diferentes, de los cuales solo la cuarta parte aproximadamente eran de alto riesgo. En nuestra serie de mujeres los tipos 6 y 11 fueron los más frecuentes de bajo riesgo, lo cual coincide a lo publicado en la literatura. En cuanto a los de alto riesgo, los de mayor frecuencia fueron los tipos 16, 31 y 33, lo cual no concuerda totalmente con las publicaciones. En nuestra serie de pacientes masculinos, el 64 por ciento de tipos de bajo riesgo fueron el 6 y el 11, lo cual es similar a lo publicado en la bibliografía estudiada. A esta diferencia entre los tipos encontrados....

To assess which are the HPV types in both male and female patients attending a private gynecological outpatient clinic. Two hundred patients were assessed: 175 women and 25 men who were diagnosed positive with HPV by visual examination, colposcopy, cytology and/or biopsy. Cervical cytology reported HPV (with or without CIN) in approximately only 40 percent of the cases, while biopsy showed this in nearly 80 percent of the cases. The typification method used for all the cases was PCR. Unidad de Ginecologia Reproduccion y Salud Integral. Valencia. More than 70 percent patients were within 15-34 years old. 60 percent of the women were nuligravidas and nulliparous. The more frequent colposcopic picture in women was acetowhite epithelium (77 percent) while all the cases of men showed warts. Detection/typification of HPV was performed by PCR in all cases with negative results in close to 10 percent women and 12 percent men. Fifteen types of HPV were found in women, in which more than half were high risk. In men only 5 different HPV types were found and only around one fourth of these cases were high risk. In our series, HPV types 6 and 11 were the low risk HPV in women, which coincides with publications in the literature. In relation to high risk HPVs, the more frequent types were 16, 31 and 33, which doesn’t coincide totally with publications. In our series of men, 64 percent of low risk were 6 and 11, which is similar to the data published in world literature. This difference between HPV types found in men and women suggests an incomplete understanding of all the factors involved in sexual transmission

Multiple novel functions of lamina associated polypeptide 2α in striated muscle.

Lamina-associated polypeptide 2α (LAP2α) is a nucleoplasmic protein that interacts with A-type lamins and the retinoblastoma protein (pRb) and affects pRb-mediated cell cycle regulation and chromatin organization. Mutations in lamin A/C and LAP2α cause late onset striated muscle diseases, but the molecular mechanisms are poorly understood. We have recently reported on the striated muscle phenotype of LAP2α-deficient mice, revealing new unexpected roles of LAP2α. Loss of LAP2α in skeletal muscle caused an upregulated stem cell-type gene expression in muscle satellite cell progeny and their delayed myogenic differentiation in vitro. In vivo, the myofiber-associated muscle stem cell pool was increased. In addition, absence of LAP2α promoted muscle remodeling towards fast myofiber types in the soleus muscle of old animals. In cardiac tissue, deletion of LAP2α caused systolic dysfunction in young mice with an increased susceptibility for fibrosis in old animals. The functional impairment in the heart was accompanied by a deregulation of major cardiac transcription factors, GATA4 and MEF2c and activation of compensatory pathways, including the downregulation of ß-adrenergic receptor signaling.Here we discuss potential functions of LAP2α in striated muscle at molecular level and how loss of these functions may cause the diverse muscle phenotypes. We propose that LAP2α serves as a transcriptional co-regulator, which controls muscle specific gene expression during muscle regeneration, muscle remodeling and stress response.

Muscle development and obesity: Is there a relationship?

The formation of skeletal muscle from the epithelial somites involves a series of events triggered by temporally and spatially discrete signals resulting in the generation of muscle fibers which vary in their contractile and metabolic nature. The fiber type composition of muscles varies between individuals and it has now been found that there are differences in fiber type proportions between lean and obese animals and humans. Amongst the possible causes of obesity, it has been suggested that inappropriate prenatal environments may 'program' the fetus and may lead to increased risks for disease in adult life. The characteristics of muscle are both heritable and plastic, giving the tissue some ability to adapt to signals and stimuli both pre and postnatally. Given that muscle is a site of fatty acid oxidation and carbohydrate metabolism and that its development can be changed by prenatal events, it is interesting to examine the possible relationship between muscle development and the risk of obesity.