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Higher-order epistasis within Pol II trigger loop haplotypes. Pol II 触发环单倍型中的高阶表观遗传。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-24 DOI: 10.1093/genetics/iyae172
Bingbing Duan, Chenxi Qiu, Steve W Lockless, Sing-Hoi Sze, Craig D Kaplan
{"title":"Higher-order epistasis within Pol II trigger loop haplotypes.","authors":"Bingbing Duan, Chenxi Qiu, Steve W Lockless, Sing-Hoi Sze, Craig D Kaplan","doi":"10.1093/genetics/iyae172","DOIUrl":"10.1093/genetics/iyae172","url":null,"abstract":"<p><p>RNA polymerase II (Pol II) has a highly conserved domain, the trigger loop (TL), that controls transcription fidelity and speed. We previously probed pairwise genetic interactions between residues within and surrounding the TL for the purpose of understand functional interactions between residues and to understand how individual mutants might alter TL function. We identified widespread incompatibility between TLs of different species when placed in the Saccharomyces cerevisiae Pol II context, indicating species-specific interactions between otherwise highly conserved TLs and its surroundings. These interactions represent epistasis between TL residues and the rest of Pol II. We sought to understand why certain TL sequences are incompatible with S. cerevisiae Pol II and to dissect the nature of genetic interactions within multiply substituted TLs as a window on higher order epistasis in this system. We identified both positive and negative higher-order residue interactions within example TL haplotypes. Intricate higher-order epistasis formed by TL residues was sometimes only apparent from analysis of intermediate genotypes, emphasizing complexity of epistatic interactions. Furthermore, we distinguished TL substitutions with distinct classes of epistatic patterns, suggesting specific TL residues that potentially influence TL evolution. Our examples of complex residue interactions suggest possible pathways for epistasis to facilitate Pol II evolution.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic prediction of cereal crop architectural traits using models informed by gene regulatory circuitries from maize. 利用玉米基因调控回路模型对谷类作物结构特征进行基因组预测。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-23 DOI: 10.1093/genetics/iyae162
Edoardo Bertolini, Mohith Manjunath, Weihao Ge, Matthew D Murphy, Mirai Inaoka, Christina Fliege, Andrea L Eveland, Alexander E Lipka
{"title":"Genomic prediction of cereal crop architectural traits using models informed by gene regulatory circuitries from maize.","authors":"Edoardo Bertolini, Mohith Manjunath, Weihao Ge, Matthew D Murphy, Mirai Inaoka, Christina Fliege, Andrea L Eveland, Alexander E Lipka","doi":"10.1093/genetics/iyae162","DOIUrl":"https://doi.org/10.1093/genetics/iyae162","url":null,"abstract":"<p><p>Plant architecture is a major determinant of planting density, which enhances productivity potential for crops per unit area. Genomic prediction is well positioned to expedite genetic gain of plant architectural traits since they are typically highly heritable. Additionally, the adaptation of genomic prediction models to query predictive abilities of markers tagging certain genomic regions could shed light on the genetic architecture of these traits. Here, we leveraged transcriptional networks from a prior study that contextually described developmental progression during tassel and leaf organogenesis in maize (Zea mays) to inform genomic prediction models for architectural traits. Since these developmental processes underlie tassel branching and leaf angle, 2 important agronomic architectural traits, we tested whether genes prioritized from these networks quantitatively contribute to the genetic architecture of these traits. We used genomic prediction models to evaluate the ability of markers in the vicinity of prioritized network genes to predict breeding values of tassel branching and leaf angle traits for 2 diversity panels in maize and diversity panels from sorghum (Sorghum bicolor) and rice (Oryza sativa). Predictive abilities of markers near these prioritized network genes were similar to those using whole-genome marker sets. Notably, markers near highly connected transcription factors from core network motifs in maize yielded predictive abilities that were significantly greater than expected by chance in not only maize but also closely related sorghum. We expect that these highly connected regulators are key drivers of architectural variation that are conserved across closely related cereal crop species.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Set2 and H3K36 regulate the Drosophila male X chromosome in a context-specific manner, independent from MSL complex spreading. Set2和H3K36以一种独立于MSL复合体扩散的特异性方式调控果蝇雄性X染色体。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-17 DOI: 10.1093/genetics/iyae168
Harmony R Salzler, Vasudha Vandadi, Julia R Sallean, A Gregory Matera
{"title":"Set2 and H3K36 regulate the Drosophila male X chromosome in a context-specific manner, independent from MSL complex spreading.","authors":"Harmony R Salzler, Vasudha Vandadi, Julia R Sallean, A Gregory Matera","doi":"10.1093/genetics/iyae168","DOIUrl":"10.1093/genetics/iyae168","url":null,"abstract":"<p><p>Dosage compensation in Drosophila involves upregulating male X-genes two-fold. This process is carried out by the MSL (male-specific lethal) complex, which binds high-affinity sites and spreads to surrounding genes. Current models of MSL spreading focus on interactions betwen MSL3 (male-specific lethal 3) and Set2-dependent histone marks like trimethylated H3 lysine-36 (H3K36me3). However, Set2 could affect DC via another target, or there could be redundancy between canonical H3.2 and variant H3.3 histones. Furthermore, it is important to parse male-specific effects from those that are X-specific. To discriminate among these possibilities, we employed genomic approaches in H3K36 'residue' and Set2 'writer' mutants. The results confirm a role for Set2 in X-gene regulation, but show that expression trends in males are often mirrored in females. Instead of global, male-specific reduction of X-genes in Set2 or H3K36 mutants, we observe heterogeneous effects. Interestingly, we identified groups of differentially expressed genes (DEGs) whose changes were in opposite directions following loss of H3K36 or Set2, suggesting that H3K36me states have reciprocal functions. In contrast to H4K16R controls, differential expression analysis of combined H3.2K36R/H3.3K36R mutants showed neither consistent reduction in X-gene expression, nor correlation with MSL3 binding. Motif analysis of the DEGs implicated BEAF-32 and other insulator proteins in Set2/H3K36-dependent regulation. Overall, the data are inconsistent with the prevailing model wherein H3K36me3 is essential for spreading the MSL complex to genes along the male X. Rather, we propose that Set2 and H3K36 support DC indirectly, via processes that are utilized by MSL but common to both sexes.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A maternal germline mutator phenotype in a family affected by heritable colorectal cancer. 一个受遗传性结直肠癌影响的家族中的母系生殖突变表型。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-15 DOI: 10.1093/genetics/iyae166
Candice L Young, Annabel C Beichman, David Mas-Ponte, Shelby L Hemker, Luke Zhu, Jacob O Kitzman, Brian H Shirts, Kelley Harris
{"title":"A maternal germline mutator phenotype in a family affected by heritable colorectal cancer.","authors":"Candice L Young, Annabel C Beichman, David Mas-Ponte, Shelby L Hemker, Luke Zhu, Jacob O Kitzman, Brian H Shirts, Kelley Harris","doi":"10.1093/genetics/iyae166","DOIUrl":"10.1093/genetics/iyae166","url":null,"abstract":"<p><p>Variation in DNA repair genes can increase cancer risk by elevating the rate of oncogenic mutation. Defects in one such gene, MUTYH, are known to elevate the incidence of colorectal cancer in a recessive Mendelian manner. Recent evidence has also linked MUTYH to a mutator phenotype affecting normal somatic cells as well as the female germline. Here, we use whole genome sequencing to measure germline de novo mutation rates in a large extended family containing both mothers and fathers who are affected by pathogenic MUTYH variation. By developing novel methodology that uses siblings as \"surrogate parents\" to identify de novo mutations, we were able to include mutation data from several children whose parents were unavailable for sequencing. In the children of mothers affected by the pathogenic MUTYH genotype p.Y179C/V234M, we identify an elevation of the C>A mutation rate that is weaker than mutator effects previously reported to be caused by other pathogenic MUTYH genotypes, suggesting that mutation rates in normal tissues may be useful for classifying cancer-associated variation along a continuum of severity. Surprisingly, we detect no significant elevation of the C>A mutation rate in children born to a father with the same MUTYH genotype, and we similarly find that the mutator effect of the mouse homolog Mutyh appears to be localized to embryonic development, not the spermatocytes. Our results suggest that maternal MUTYH variants can cause germline mutations by attenuating the repair of oxidative DNA damage in the early embryo.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mutation potentiates migration swamping in polygenic local adaptation. 突变会加剧多基因局部适应中的迁移沼泽化。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-12 DOI: 10.1093/genetics/iyae165
Takahiro Sakamoto, James R Whiting, Samuel Yeaman
{"title":"Mutation potentiates migration swamping in polygenic local adaptation.","authors":"Takahiro Sakamoto, James R Whiting, Samuel Yeaman","doi":"10.1093/genetics/iyae165","DOIUrl":"10.1093/genetics/iyae165","url":null,"abstract":"<p><p>Locally adapted traits can exhibit a wide range of genetic architectures, from pronounced divergence at a few loci to small frequency divergence at many loci. The type of architecture that evolves depends strongly on the migration rate, as weakly selected loci experience swamping and do not make lasting contributions to divergence. Simulations from previous studies showed that even when mutations are strongly selected and should resist migration swamping, the architecture of adaptation can collapse and become transient at high mutation rates. Here, we use an analytical two-population model to study how this transition in genetic architecture depends upon population size, strength of selection, and parameters describing the mutation process. To do this, we develop a mathematical theory based on the diffusion approximation to predict the threshold mutation rate above which the transition occurs. We find that this performs well across a wide range of parameter space, based on comparisons with individual-based simulations. The threshold mutation rate depends most strongly on the average effect size of mutations, weakly on the strength of selection, and marginally on the population size. Across a wide range of the parameter space, we observe that the transition to a transient architecture occurs when the trait-wide mutation rate is 10-3-10-2, suggesting that this phenomenon is potentially relevant to complex traits with a large mutational target. On the other hand, based on the apparent stability of genetic architecture in many classic examples of local adaptation, our theory suggests that per-trait mutation rates are often relatively low.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Dominance Hypothesis Argument for Historical Genetic Gains and the Fixation of Heterosis in Octoploid Strawberry. 八倍体草莓历史遗传增益和杂交固定的优势假说论证
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-10 DOI: 10.1093/genetics/iyae159
Mitchell J Feldmann, Dominique D A Pincot, Danelle K Seymour, Randi A Famula, Nicolás P Jiménez, Cindy M López, Glenn S Cole, Steven J Knapp
{"title":"A Dominance Hypothesis Argument for Historical Genetic Gains and the Fixation of Heterosis in Octoploid Strawberry.","authors":"Mitchell J Feldmann, Dominique D A Pincot, Danelle K Seymour, Randi A Famula, Nicolás P Jiménez, Cindy M López, Glenn S Cole, Steven J Knapp","doi":"10.1093/genetics/iyae159","DOIUrl":"10.1093/genetics/iyae159","url":null,"abstract":"<p><p>Heterosis was the catalyst for the domestication of cultivated strawberry (Fragaria × ananassa), an interspecific hybrid species that originated in the 1700s. The hybrid origin was discovered because the phenotypes of spontaneous hybrids transgressed those of their parent species. The transgressions included fruit yield increases and other genetic gains in the twentieth century that sparked the global expansion of strawberry production. The importance of heterosis to the agricultural success of the hybrid species, however, has remained a mystery. Here we show that heterosis has disappeared (become fixed) among improved hybrids within a population (the California population) that has been under long-term selection for increased fruit yield, weight, and firmness. We found that the highest yielding hybrids are among the most highly inbred (59-79%), which seems counterintuitive for a highly heterozygous, outbreeder carrying heavy genetic loads. Although faint remnants of heterosis were discovered, the between-parent allele frequency differences and dispersed favorable dominant alleles necessary for heterosis have decreased nearly genome-wide within the California population. Conversely, heterosis was prevalent and significant among wide hybrids, especially for fruit count, a significant driver of genetic gains for fruit yield. We attributed the disappearance (fixation) of heterosis within the California population to increased homozygosity of favorable dominant alleles and inbreeding associated with selection, random genetic drift, and selective sweeps. Despite historical inbreeding, the highest yielding hybrids reported to-date are estimated to be heterozygous for 20,370-44,280 of 97,000-108,000 genes in the octoploid genome, the equivalent of an entire diploid genome or more.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Location of polyadenylation sites within 3' untranslated regions is linked to biological function in yeast. 多腺苷酸化位点在 3' 非翻译区内的位置与酵母的生物功能有关。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-09 DOI: 10.1093/genetics/iyae163
Joseph V Geisberg, Zarmik Moqtaderi, Kevin Struhl
{"title":"Location of polyadenylation sites within 3' untranslated regions is linked to biological function in yeast.","authors":"Joseph V Geisberg, Zarmik Moqtaderi, Kevin Struhl","doi":"10.1093/genetics/iyae163","DOIUrl":"10.1093/genetics/iyae163","url":null,"abstract":"<p><p>Expression of a typical yeast gene results in ∼50 3' mRNA isoforms that are distinguished by the locations of poly(A) sites within the 3' untranslated regions (3' UTRs). The location of poly(A) sites with respect to the translational termination codon varies considerably among genes, but whether this has any functional significance is poorly understood. Using hierarchical clustering of 3' UTRs, we identify eight classes of S. cerevisiae genes based on their poly(A) site locations. Genes involved in related biological functions (GO categories) are uniquely over-represented in six of these classes. Similar analysis of S. pombe genes reveals three classes of 3' UTRs, all of which show over-representation of functionally related genes. Remarkably, S. cerevisiae and S. pombe homologs share related patterns of poly(A) site locations. These observations suggest that the location of poly(A) sites within 3' UTRs has biological significance.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative analysis of new mScarlet-based red fluorescent tags in Caenorhabditis elegans. 基于 mScarlet 的新型红色荧光标记在秀丽隐杆线虫中的比较分析。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-07 DOI: 10.1093/genetics/iyae126
Wen Xi Cao, Daniel M Merritt, Karinna Pe, Michael Cesar, Oliver Hobert
{"title":"Comparative analysis of new mScarlet-based red fluorescent tags in Caenorhabditis elegans.","authors":"Wen Xi Cao, Daniel M Merritt, Karinna Pe, Michael Cesar, Oliver Hobert","doi":"10.1093/genetics/iyae126","DOIUrl":"10.1093/genetics/iyae126","url":null,"abstract":"<p><p>One problem that has hampered the use of red fluorescent proteins in the fast-developing nematode Caenorhabditis elegans has been the substantial time delay in maturation of several generations of red fluorophores. The recently described mScarlet-I3 protein has properties that may overcome this limitation. We compare here the brightness and onset of expression of CRISPR/Cas9 genome-engineered mScarlet, mScarlet3, mScarlet-I3, and GFP reporter knock-ins. Comparing the onset and brightness of expression of reporter alleles of C. elegans golg-4, encoding a broadly expressed Golgi resident protein, we found that the onset of detection of mScarlet-I3 in the embryo is several hours earlier than older versions of mScarlet and comparable to GFP. These findings were further supported by comparing mScarlet-I3 and GFP reporter alleles for pks-1, a gene expressed in the CAN neuron and cells of the alimentary system, as well as reporter alleles for the pan-neuronal, nuclear marker unc-75. Hence, the relative properties of mScarlet-I3 and GFP do not depend on cellular or subcellular context. In all cases, mScarlet-I3 reporters also show improved signal-to-noise ratio compared to GFP.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adapting and optimizing GCaMP8f for use in Caenorhabditis elegans. 调整和优化 GCaMP8f,使其用于秀丽隐杆线虫。
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-07 DOI: 10.1093/genetics/iyae125
Jun Liu, Elsa Bonnard, Monika Scholz
{"title":"Adapting and optimizing GCaMP8f for use in Caenorhabditis elegans.","authors":"Jun Liu, Elsa Bonnard, Monika Scholz","doi":"10.1093/genetics/iyae125","DOIUrl":"10.1093/genetics/iyae125","url":null,"abstract":"<p><p>Improved genetically encoded calcium indicators (GECIs) are essential for capturing intracellular dynamics of both muscle and neurons. A novel set of GECIs with ultrafast kinetics and high sensitivity was recently reported by Zhang et al. (2023). While these indicators, called jGCaMP8, were demonstrated to work in Drosophila and mice, data for Caenorhabditis elegans were not reported. Here, we present an optimized construct for C. elegans and use this to generate several strains expressing GCaMP8f (fast variant of the indicator). Utilizing the myo-2 promoter, we compare pharyngeal muscle activity measured with GCaMP7f and GCaMP8f and find that GCaMP8f is brighter upon binding to calcium, shows faster kinetics, and is not disruptive to the intrinsic contraction dynamics of the pharynx. Additionally, we validate its application for detecting neuronal activity in touch receptor neurons which reveals robust calcium transients even at small stimulus amplitudes. As such, we establish GCaMP8f as a potent tool for C. elegans research which is capable of extracting fast calcium dynamics at very low magnifications across multiple cell types.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neurogenesis in Caenorhabditis elegans. 秀丽隐杆线虫的神经发生
IF 3.3 3区 生物学
Genetics Pub Date : 2024-10-07 DOI: 10.1093/genetics/iyae116
Richard J Poole, Nuria Flames, Luisa Cochella
{"title":"Neurogenesis in Caenorhabditis elegans.","authors":"Richard J Poole, Nuria Flames, Luisa Cochella","doi":"10.1093/genetics/iyae116","DOIUrl":"10.1093/genetics/iyae116","url":null,"abstract":"<p><p>Animals rely on their nervous systems to process sensory inputs, integrate these with internal signals, and produce behavioral outputs. This is enabled by the highly specialized morphologies and functions of neurons. Neuronal cells share multiple structural and physiological features, but they also come in a large diversity of types or classes that give the nervous system its broad range of functions and plasticity. This diversity, first recognized over a century ago, spurred classification efforts based on morphology, function, and molecular criteria. Caenorhabditis elegans, with its precisely mapped nervous system at the anatomical level, an extensive molecular description of most of its neurons, and its genetic amenability, has been a prime model for understanding how neurons develop and diversify at a mechanistic level. Here, we review the gene regulatory mechanisms driving neurogenesis and the diversification of neuron classes and subclasses in C. elegans. We discuss our current understanding of the specification of neuronal progenitors and their differentiation in terms of the transcription factors involved and ensuing changes in gene expression and chromatin landscape. The central theme that has emerged is that the identity of a neuron is defined by modules of gene batteries that are under control of parallel yet interconnected regulatory mechanisms. We focus on how, to achieve these terminal identities, cells integrate information along their developmental lineages. Moreover, we discuss how neurons are diversified postembryonically in a time-, genetic sex-, and activity-dependent manner. Finally, we discuss how the understanding of neuronal development can provide insights into the evolution of neuronal diversity.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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