Project description:Note: this project is a combination of the data deposited here in GEO and data made available by HDBR in ArrayExpress under E-MTAB-4840. Summary: Brain asymmetry in humans, both structurally and functionally, is observed very early during development, and is important for healthy development. Using RNA sequencing, we investigated gene expression profiles of left and right sides of various brain structures in human foetuses aged 5 to 13 weeks post conception. All brain structures showed significant differences between the expression profiles of left and right sides. The differences partly correlated with gene expression changes with age, suggesting left/right differences in maturation rate. In particular on the faster side (right for cerebral cortex, left for all other investigated tissues), different tissues were lateralised for tissue-specific processes. In the youngest forebrain (5.5 weeks), KCTD12, SNAI1 and GATA1 were significantly right-lateralised. SNAI1 is involved in visceral asymmetry in vertebrates, and KCTD12 is important in lateralisation of fish brains. In the youngest midbrain, SOX1 was significantly left-lateralised.
Project description:Left-right asymmetry is a basic character of aging brain; however, the molecular foundation of the left-right asymmetry remains unclear. The morphology, physiology and behavior of rhesus aging are obviously similar to human aging, but the aging-rate of rhesus is roughly three times as fast as human, in which the underlying mechanism needs further investigation. By using of 6-plex tandem mass tag (TMT) labeling, we presented a high throughput quantitative proteomics analysis to 6 group hippocampal samples including left and right hippocampus from 3 years, 6 years and 20 years old rhesus. Our data identified 3391 high-confidence proteins. After screening, we found 340 aging-related proteins of left hippocampus and 334 aging-related proteins of right hippocampus, in which there were 114 overlap proteins. Furthermore, the aging-related proteome of left rhesus hippocampus aging was compared with human aging-related proteome of left hippocampus that was reported by our lab previously. As the results show, we discovered 446 aging-related proteins in rhesus and 830 aging-related proteins in human with an overlap of 106 proteins.
Project description:The brain is a functionally complex organ, the patterning and development of which are key to adult health. To help elucidate the genetic networks underlying mammalian brain patterning we conducted detailed transcriptional profiling during embryonic development of the mouse brain. 2400 genes were identified as showing differential expression between three developmental stages. Analysis of the data identified nine gene clusters to demonstrate analogous expression profiles. A significant group of novel genes of as yet undiscovered biological function were detected, as being potentially relevant to brain development and function, in addition to genes that have previously identified roles in the brain. Analysis of left-right asymmetry of expression revealed 35 genes as putatively asymmetric from a combined data set. Our data constitutes a valuable new resource for neuroscience and neuro-development, exposing possible functional associations between genes, including novel loci, and encouraging their further investigation in human neurological and behavioural disorders. Whole genome transcriptional profiling carried out on 24 samples during 3 stages of embryonic development of the mouse brain was carried out with matching left-right asymmetry on four biological replicates at each stage.
Project description:Left-right asymmetry is a fundamental organizing feature of the human brain, and neuro-psychiatric disorders such as schizophrenia sometimes involve alterations of brain asymmetry. As early as 8 weeks post conception, the majority of human foetuses move their right arms more than their left arms, but because nerve fibre tracts are still descending from the forebrain at this stage, spinal-muscular asymmetries are likely to play an important developmental role. Here we have used gene expression profiling in 18 human embryos to show that the left side of the human spinal cord, between four and eight weeks post conception, matures slightly faster than the right side, even though both sides transition from transcriptional profiles associated with cell division and proliferation at earlier stages, to later neuronal differentiation and function. The hindbrain showed a left-right mirrored pattern compared to the spinal cord.
Project description:Structural birth defects are the leading cause of infant mortality in the United States. Many of these defects are associated with abnormal anatomical left-right asymmetry. Despite the importance of orienting organs along the left-right (L-R) axis during development, very little is known about the molecular events that control this process. To elucidate the genetic mechanisms that shape the L-R asymmetry of individual organs, we sought to identify genes that are expressed in L-R asymmetric patterns during organ development. To accomplish this goal, we took advantage of the exceptionally large Budgett’s frog (Lepidobatrachus laevis) embryo to profile gene expression by RNA-seq in the left versus right halves of the developing stomach. Using this data, we have constructed a de novo Lepidobatrachus transcriptome and identified ~26,000 unique transcripts with human homology based on reciprocal BLAST analyses. Over 300 transcripts were L-R asymmetrically expressed within the stomach. Among these candidates are some of the few genes already known to play a role in L-R asymmetric development, validating our strategy for L-R gene discovery.
Project description:Left and Right phrenic nerves, which innervate the left and right diaphragm muscles, exhibit different innervation patterns. This left/right (L/R) asymmetry is established at the onset of innervation by a developmental program that requires Nodal. Phenotype analysis suggests that the cervical motoneurons, which innervate the diaphragm, have a L/R imprint that contributes to set the L/R asymmetries of innervation. We used microarray to analyze the expression profile of left and right cervical motoneurons before diaphragm innervation
Project description:Non-syndromic facial asymmetry is commonly found in dentofacial deformity populations with skeletal malocclusions. Asymmetry of this type may result from imbalanced growth and function of both the jaw and associated muscles. Among the multiple genes that interact to affect the craniofacial musculoskeletal complex during pre and postnatal growth and development, NODAL signaling pathwy (NSP) genes are active in adult skeletal muscle and may be key factors in development, growth and maintenance of facial asymmetry. It is of interest to determine whether expression of NODAL pathway genes might differ in masseter muscles between individuals with malocclusion that have facial asymmetry and normal symmetry. Human Transcriptome 2.0 GeneChips (HTA2.0) were used to examine global gene expression in masster muscles between malocclusion subjects with posterior facial asymmetry and with normal facial symmetry. Eleven patients undergoing orthoganthic surgery were selected for comparison of masseter muscle gene expression on microarrays. Two subjects had posterior facial asymmetry (one with class II open bite and one with class III open bite malocclusion) and nine subjects had normal facial symmetry (three with class II open bite, two with class III open bite and four with class II deep bite malocclusion). RNA representative of total gene expression in masseter muscles of the malocclusion subjects with and without posterior facial asymmetry was prepared for labeling and hybridization on HTA2.0 chips. The two subjects with facial asymmetry clustered separately from eight other malocclusion subjects by a principle component analysis (PCA), even though one had a class II and the other a class III malocclusion. Sample 4L_Open_II is from a subject who has sleep apnea. Data from 4L_Open_II clustered independent of the asymmetry group and the eight other subjects of the symmetry group by PCA and was not included in analysis of differential expression with facial symmetry. Masseter muscles are paired jaw muscles (i.e. right and left masseter). In some cases, there was not sufficient quantity/quality of RNA from one side, thus the other side was used. Please note that the following information is provided in the 'source name' field of each sample record; subject ID number; either left or right masseter; J CRANIOFAC SURG_ID# corresponding to the data presented in the manuscript
Project description:The brain is a functionally complex organ, the patterning and development of which are key to adult health. To help elucidate the genetic networks underlying mammalian brain patterning we conducted detailed transcriptional profiling during embryonic development of the mouse brain. 2400 genes were identified as showing differential expression between three developmental stages. Analysis of the data identified nine gene clusters to demonstrate analogous expression profiles. A significant group of novel genes of as yet undiscovered biological function were detected, as being potentially relevant to brain development and function, in addition to genes that have previously identified roles in the brain. Analysis of left-right asymmetry of expression revealed 35 genes as putatively asymmetric from a combined data set. Our data constitutes a valuable new resource for neuroscience and neuro-development, exposing possible functional associations between genes, including novel loci, and encouraging their further investigation in human neurological and behavioural disorders.
2014-03-01 | GSE44932 | GEO
Project description:MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates
Project description:<p>Heterotaxy syndrome is a congenital anomaly syndrome accompanied by thoracic and abdominal situs abnormalities. The study cohort comprises of individuals with heterotaxy or related congenital heart disease (CHD) who have undergone exome sequencing. The purpose of the study is to elucidate the molecular genetics of the disorder as well as contribute to knowledge about the biology of normal and abnormal development of left-right anatomic asymmetry. These results will further help delineate genotype-phenotype associations and provide important information on the causes, management, and prognosis of heterotaxy syndrome.</p>