Epidermal Development Research Articles

Epidermal Patterning Factor 2-like (McEPFL2): A Putative Candidate for the Continuous Ridge (cr) Fruit Skin Locus in Bitter Gourd (Momordica charantia L.).

Bitter gourd (Momordica charantia L.) is an economically important vegetable and medicinal crop in many Asian countries. Limited work has been conducted in understanding the genetic basis of horticulturally important traits in bitter gourd. Bitter gourd is consumed primarily for its young, immature fruit, and fruit appearance plays an important role in market acceptability. One such trait is the ridges on the fruit skin. In the present study, molecular mapping of a locus underlying fruit ridge continuity was conducted. Genetic analysis in segregating populations, derived from the crosses between two inbred lines Y1 with continuous ridges (CR) and Z-1-4 with discontinuous ridges (DCR), suggested that CR was controlled by a single recessive gene (cr). High-throughput genome sequencing of CR and DCR bulks combined with high-resolution genetic mapping in an F2 population delimited cr into a 108 kb region with 16 predicted genes. Sequence variation analysis and expression profiling supported the epidermal patterning factor 2-like (McEPFL2) gene as the best candidate of the cr locus. A 1 bp deletion in the first exon of McEPFL2 in Y1 which would result in a truncated McEPFL2 protein may be the causal polymorphism for the phenotypic difference between Y1 and Z-1-4. The association of this 1 bp deletion with CR was further supported by gDNA sequencing of McEPFL2 among 31 bitter gourd accessions. This work provides a foundation for understanding the genetic and molecular control of fruit epidermal pattering and development, which also facilitates marker-assisted selection in bitter melon breeding.

Anillin governs mitotic rounding during early epidermal development

BackgroundThe establishment of tissue architecture requires coordination between distinct processes including basement membrane assembly, cell adhesion, and polarity; however, the underlying mechanisms remain poorly understood. The actin cytoskeleton is ideally situated to orchestrate tissue morphogenesis due to its roles in mechanical, structural, and regulatory processes. However, the function of many pivotal actin-binding proteins in mammalian development is poorly understood.ResultsHere, we identify a crucial role for anillin (ANLN), an actin-binding protein, in orchestrating epidermal morphogenesis. In utero RNAi-mediated silencing of Anln in mouse embryos disrupted epidermal architecture marked by adhesion, polarity, and basement membrane defects. Unexpectedly, these defects cannot explain the profoundly perturbed epidermis of Anln-depleted embryos. Indeed, even before these defects emerge, Anln-depleted epidermis exhibits abnormalities in mitotic rounding and its associated processes: chromosome segregation, spindle orientation, and mitotic progression, though not in cytokinesis that was disrupted only in Anln-depleted cultured keratinocytes. We further show that ANLN localizes to the cell cortex during mitotic rounding, where it regulates the distribution of active RhoA and the levels, activity, and structural organization of the cortical actomyosin proteins.ConclusionsOur results demonstrate that ANLN is a major regulator of epidermal morphogenesis and identify a novel role for ANLN in mitotic rounding, a near-universal process that governs cell shape, fate, and tissue morphogenesis.

Gene network analysis reveals candidate genes related with the hair follicle development in sheep

BackgroundMerino sheep are the most famous fine wool sheep in the world. They have high wool production and excellent wool quality and have attracted worldwide attention. The fleece of the Merino sheep is composed predominantly of wool fibers grown from secondary wool follicles. Therefore, it is necessary to study the development of hair follicles to understand the mechanism of wool production. The hair follicle is a complex biological system involved in a dynamic process governed by gene regulation. The hair follicle development process is very complex and poorly understood. The purpose of our research is to identify candidate genes related to hair follicle development, provide a theoretical molecular breeding basis for the cultivation of fine wool sheep, and provide a reference for the problems of hair loss and alopecia areata that affect human beings.ResultsWe analyzed mRNAs data in skin tissues of 18 Merino sheep at four embryonic days (E65, E85, E105 and E135) and two postnatal days (P7 and P30). G1 to G6 represent hair follicles developmental at six stages (i.e. E65 to P30). We identified 7879 differentially expressed genes (DEGs) and 12623 novel DEGs, revealed different expression patterns of these DEGs at six stages of hair follicle development, and demonstrated their complex interactions. DEGs with stage-specific expression were significantly enriched in epidermal differentiation and development, hair follicle development and hair follicle morphogenesis and were enriched in many pathways related to hair follicle development. The key genes (LAMA5, WNT10A, KRT25, SOSTDC1, ZDHHC21, FZD1, BMP7, LRP4, TGFβ2, TMEM79, SOX10, ITGB4, KRT14, ITGA6, and GLI2) affecting hair follicle morphogenesis were identified by network analysis.ConclusionThis study provides a new reference for the molecular basis of hair follicle development and lays a foundation for further improving sheep hair follicle breeding. Candidate genes related to hair follicular development were found, which provided a theoretical basis for molecular breeding for the culture of fine wool sheep. These results are a valuable resource for biological investigations of fleece evolution in animals.

Alleles of unc-33/CRMP exhibit defects during Caenorhabditis elegans epidermal morphogenesis.

Microtubule-associated proteins regulate the dynamics, organization, and function of microtubules, impacting a number of vital cellular processes. CRMPs have been shown to control microtubule assembly and axon outgrowth during neuronal differentiation. While many microtubule-associated proteins have been linked to roles in cell division and neuronal development, it is still unclear the complement that control the formation of parallel microtubule arrays in epithelial cells. Here we show through time-lapse DIC microscopy that Caenorhabditis elegans embryos homozygous for the weak loss-of-function allele unc-33(e204) progress more slowly through epidermal morphogenesis, while animals homozygous for strong loss-of-function alleles exhibit more embryonic lethality. Identification of two novel missense mutations in unc-33(e572), Val476Gly, and Ser731Thr, lead to computational approaches to determine the potential effects of these changes on UNC-33/CRMP structure. Molecular dynamics simulations show that for Asp389Asn and Arg502His, two other known missense mutations, local changes in protein-protein hydrogen bonding affect the stability of the protein. However, the Val476Gly/Ser731Thr combination does not alter the structure or energetics of UNC-33 drastically when compared to the wild-type protein. These results support a novel role for UNC-33/CRMP in C. elegans epidermal development and shed light on how individual amino acid changes cause a loss-of-function in UNC-33.

Treatment Strategies for Non-Small Cell Lung Cancer Harboring Common and Uncommon EGFR Mutations: Drug Sensitivity Based on Exon Classification, and Structure-Function Analysis.

Simple SummaryThe advent of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) has led to a dramatic improvement in the prognosis of patients having advanced EGFR-mutant non-small cell lung cancer (NSCLC). NSCLCs harboring “common” EGFR mutations, including exon 19 deletions and exon 21 L858R mutation substitutions, are sensitive to EGFR-TKIs. However, NSCLCs harboring “uncommon” EGFR mutations have poor sensitivity to EGFR-TKIs, and patients harboring uncommon mutations often experience poor outcomes. Here, we review the current EGFR-TKI therapy and the development of treatment strategies, including combined treatment and the exploration of new drugs. In addition, we discuss EGFR-TKI sensitivity based on structure-function analysis.The identification of epidermal growth factor receptor (EGFR) mutations and development of EGFR tyrosine kinase inhibitors (EGFR-TKIs) have dramatically improved the prognosis of advanced EGFR-mutated non-small cell lung cancer (NSCLC), setting a landmark in precision oncology. Exon 19 deletions and exon 21 L858R substitutions, which comprise the majority of common EGFR mutations, are predictors of good sensitivity to EGFR-TKIs. However, not all cancers harboring EGFR mutations are sensitive to EGFR-TKIs. Most patients harboring uncommon EGFR mutations demonstrate a poorer clinical response than those harboring common EGFR mutations. For example, cancers harboring exon 20 insertions, which represent approximately 4–12% of EGFR mutations, are generally insensitive to first- and second-generation EGFR-TKIs. Although understanding the biology of uncommon EGFR mutations is essential for developing treatment strategies, there is little clinical data because of their rarity. Moreover, clarifying the acquired resistance of EGFR-mutated NSCLC may lead to more precise treatments. Sequencing and structure-based analyses of EGFRmutated NSCLC have revealed resistance mechanisms and drug sensitivity. In this review, we discuss the strategies in development for treating NSCLC harboring common and uncommon EGFR mutations. We will also focus on EGFR-TKI sensitivity in patients harboring EGFR mutations based on the structural features.

Genome-Wide Identification and Expression Analysis of Homeodomain Leucine Zipper Subfamily IV (HD-ZIP IV) Gene Family in Cannabis sativa L.

The plant-specific homeodomain zipper family (HD-ZIP) of transcription factors plays central roles in regulating plant development and environmental resistance. HD-ZIP transcription factors IV (HDZ IV) have been involved primarily in the regulation of epidermal structure development, such as stomata and trichomes. In our study, we identified nine HDZ IV-encoding genes in Cannabis sativa L. by conducting a computational analysis of cannabis genome resources. Our analysis suggests that these genes putatively encode proteins that have all the conserved domains of HDZ IV transcription factors. The phylogenetic analysis of HDZ IV gene family members of cannabis, rice (Oryza sativa), and Arabidopsis further implies that they might have followed distinct evolutionary paths after divergence from a common ancestor. All the identified cannabis HDZ IV gene promoter sequences have multiple regulation motifs, such as light- and hormone-responsive elements. Furthermore, experimental evidence shows that different HDZ IV genes have different expression patterns in root, stem, leaf, and flower tissues. Four genes were primarily expressed in flowers, and the expression of CsHDG5 (XP_030501222.1) was also correlated with flower maturity. Fifty-nine genes were predicted as targets of HDZ IV transcription factors. Some of these genes play central roles in pathogen response, flower development, and brassinosteroid signaling. A subcellular localization assay indicated that one gene of this family is localized in the Arabidopsis protoplast nucleus. Taken together, our work lays fundamental groundwork to illuminate the function of cannabis HDZ IV genes and their possible future uses in increasing cannabis trichome morphogenesis and secondary metabolite production.

Analysis of the Expression and Role of Keratin 17 in Human Tumors.

Objective: We aimed to explore the expression and carcinogenic effect of KRT17 in human tumors and provide useful information for the study of KRT17. Methods: We used databases including the Cancer Genome Atlas, Gene Expression Omnibus, GTEx, and GEPIA2 to analyze the expression, mutation, and prognosis of KRT17 in human tumors. Through webservers, including UALCAN, TIMER2.0, and STRING, we learned about the genetic variation, immune cell penetration, and enrichment analysis of KRT17-related genes. Results: KRT17 was highly expressed in most tumors (such as esophageal cancer, lung cancer, cervical cancer, etc.), and the high expression level correlated with tumor stage and prognosis. In addition, amplification was the main type of KRT17 tumor variation, with an amplification rate of about 9%, followed by mutation, with a mutation rate of 4%. Moreover, KRT17 was strongly associated with tumor-infiltrating immune cells (such as macrophages, CD8+T, Tregs, and cancer-associated fibroblasts). KEGG analysis suggested that KRT17 may play a role in tumor pathogenesis following human papillomavirus infection, and the gene ontology enrichment analysis indicated that the carcinogenicity of KRT17 can be attributed to cadherin binding, intermediate fibrocytoskeleton and epidermal development. Conclusion: KRT17 may play an important role in the occurrence, development, and prognosis of malignant tumors. We provided a relatively comprehensive description of the carcinogenic role of KRT17 in different tumors for the first time.

TRY intron2 determined its expression in inflorescence activated by SPL9 and MADS-box genes in Arabidopsis

Plant trichomes are specialized epidermal cells that protect plants from insects and pathogens. In Arabidopsis, epidermal hairs decrease as internodes increase in height, with only few epidermal hairs produced on the sepals abaxial surface of the early flowers. TRIPTYCHON (TRY) is known to be a negative regulator of epidermal hair development in Arabidopsis, suppressing the formation of ectopic epidermal hairs in the inflorescence. Here, we reported that the second intron of TRY gene plays a critical role in trichome spatial distribution in Arabidopsis. The expression of TRY rises with the increasing stem nodes and reaches the peak in the inflorescence, while the trichomes distribution decrease. The transgenic plants showed that TRY promoter could only drive the genomic instead of coding sequences combined with GUS reporter gene, which indicates that the regulatory elements of TRY expression in inflorescence could be located in the intron regions. Multiple SPLs and MADS-box binding sites were found in the TRY intron2 sequence. Further genetic and biochemistry assays revealed that the flowering-related genes such as SPL9 could bind to these cis-elements directly, contributing to the TRY spatial expression. Since cotton fiber and Arabidopsis trichomes share similar regulatory mechanism, extended analysis showed that the intron2 of cotton TRY genes also contain the cis-elements. Thus, the introns harboring the transcription element may be the general way to regulate the gene expression in different plants and provides molecular clues for the related crops’ traits design.

Epigenetic Mechanisms of Epidermal Differentiation.

Keratinocyte differentiation is an essential process for epidermal stratification and stratum corneum formation. Keratinocytes proliferate in the basal layer of the epidermis and start their differentiation by changing their functional or phenotypical type; this process is regulated via induction or repression of epidermal differentiation complex (EDC) genes that play a pivotal role in epidermal development. Epidermal development and the keratinocyte differentiation program are orchestrated by several transcription factors, signaling pathways, and epigenetic regulators. The latter exhibits both activating and repressive effects on chromatin in keratinocytes via the ATP-dependent chromatin remodelers, histone demethylases, and genome organizers that promote terminal keratinocyte differentiation, and the DNA methyltransferases, histone deacetylases, and Polycomb components that stimulate proliferation of progenitor cells and inhibit premature activation of terminal differentiation-associated genes. In addition, microRNAs are involved in different processes between proliferation and differentiation during the program of epidermal development. Here, we bring together current knowledge of the mechanisms controlling gene expression during keratinocyte differentiation. An awareness of epigenetic mechanisms and their alterations in health and disease will help to bridge the gap between our current knowledge and potential applications for epigenetic regulators in clinical practice to pave the way for promising target therapies.

Identification of the potential biological target molecules related to primary open-angle glaucoma

BackgroundTo identify the potential biological target molecules and the corresponding interaction networks in primary open-angle glaucoma (POAG) development.MethodsThe microarray datasets of GSE138125 and GSE27276 concerning lncRNA and mRNA expression profiles in trabecular meshwork of POAG were downloaded from the Gene Expression Omnibus database. The R software was applied to identify differentially expressed (DE) lncRNAs and mRNAs in POAG, and to perform GO and KEGG functional enrichment analysis. Protein–protein interaction (PPI) network and module analysis, and lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network were performed by Cytoscape software.ResultsA total of 567 DE-mRNAs were identified from GSE138125 and GSE27276, including 298 up-regulated and 269 down-regulated mRNAs, which were found enriching in biological processes of extracellular matrix organization and epidermis development, respectively. KEGG pathway enrichment analysis further revealed that module genes in PPI network were primarily involved in the AGE-PAGE, PI3K-Akt and TGF-β signaling pathways. Moreover, 897 up-regulated and 1036 down-regulated DE-lncRNAs were identified from GSE138125. Through literature review and databases searching, we obtained 712 lncRNA-miRNA and 337 miRNA-mRNA pairs based on the selected eight POAG-related miRNAs. After excluding 702 lncRNAs and 284 mRNAs that were not comprised in the DE-lncRNA and DE-mRNAs, a total of 53 lncRNA nodes, eight miRNA nodes, 10 mRNA nodes, and 78 edges were included in the final ceRNA network.ConclusionsThis study demonstrated the lncRNA and mRNA expression profiles of trabecular meshwork in POAG patients and the normal controls, and identified potentially ceRNAs and pathways which might improve the pathogenic understanding of this ocular disease.

C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8

Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. The aECM is highly dynamic and constantly undergoes remodeling during animal development. How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition.

An analysis of skin thickness in the Dezhou donkey population and identification of candidate genes by RNA-seq.

The aim of the present study was to analyze the main factors that have a significant impact on skin thickness, and to further identify the genes and signaling pathways regulating skin growth by RNA-seq in Dezhou donkeys. Skin samples from different body regions of 15 slaughtered donkeys were obtained to study variations in skin thickness over the bodies. Skin thickness data for another 514 donkeys was obtained by minimally invasive skin sampling from the back, and measurements of the donkeys' body size traits and pedigree data were also collected. These data were used to analyze changes in skin thickness and estimate genetic parameters. In addition, transcriptomic analysis was conducted on the skin tissues of individuals from two groups with significant differences in skin thickness. Our results showed that skin thickness over the bodies ranged from 1.08 to 4.36mm. The skin from the back was the thickest and had the highest correlation with that of other regions of the body. The skin thickness decreased from the back to the side of the ventral abdomen, and the skin thickness on the limbs increased from the proximal end to the distal end. The results also showed that the skin from the same body regions of jacks was thicker than that of jennies in the same age group. The skin thickness of jennies increased from birth to the age of 2 and then clearly decreased after 2years of age. The estimated heritability of skin thickness was 0.15, and the genetic correlations between skin thickness and body size traits were negligible. Transcriptome analysis showed that the thick-skin group had 65 up-regulated genes and 38 down-regulated genes compared with the thin-skin group. The differentially expressed genes were highly enriched in epidermal development and cell adhesion molecule signaling pathways. We identified the candidate genes responsible for variations in skin thickness in the Dezhou donkey, including KRT10, KRT1, CLDN9, MHCII and MMP28. These results contribute to a better understanding of the growth and development of donkey skin, reveal the molecular mechanism responsible for donkey skin thickness and suggest directions for genetic selection in the Dezhou donkey population.

Identification of the Regulators of Epidermis Development under Drought- and Salt-Stressed Conditions by Single-Cell RNA-Seq.

As sessile organisms, plants constantly face challenges from the external environment. In order to meet these challenges and survive, plants have evolved a set of sophisticated adaptation strategies, including changes in leaf morphology and epidermal cell development. These developmental patterns are regulated by both light and hormonal signaling pathways. However, our mechanistic understanding of the role of these signaling pathways in regulating plant response to environmental stress is still very limited. By applying single-cell RNA-Seq, we determined the expression pattern of PHYTOCHROME INTERACTING FACTOR (PIF) 1, PIF3, PIF4, and PIF5 genes in leaf epidermal pavement cells (PCs) and guard cells (GCs). PCs and GCs are very sensitive to environmental stress, and our previous research suggests that these PIFs may be involved in regulating the development of PCs, GCs, and leaf morphology under environmental stress. Growth analysis showed that pif1/3/4/5 quadruple mutant maintained tolerance to drought and salt stress, and the length to width ratio of leaves and petiole length under normal growth conditions were similar to those of wild-type (WT) plants under drought and salt treatment. Analysis of the developmental patterns of PCs and GCs, and whole leaf morphology, further confirmed that these PIFs may be involved in mediating the development of epidermal cells under drought and salt stress, likely by regulating the expression of MUTE and TOO MANY MOUTHS (TMM) genes. These results provide new insights into the molecular mechanism of plant adaptation to adverse growth environments.

Decay of TRPV3 as the genomic trace of epidermal structure changes in the land-to-sea transition of mammals.

The epidermis plays an indispensable barrier function in animals. Some species have evolved unique epidermal structures to adapt to different environments. Aquatic and semi‐aquatic mammals (cetaceans, manatees, and hippopotamus) are good models to study the evolution of epidermal structures because of their exceptionally thickened stratum spinosum, the lack of stratum granulosum, and the parakeratotic stratum corneum. This study aimed to analyze an upstream regulatory gene transient receptor potential cation channel, subfamily V, member 3 (TRPV3) of epidermal differentiation so as to explore the association between TRPV3 evolution and epidermal changes in mammals. Inactivating mutations were detected in almost all the aquatic cetaceans and several terrestrial mammals. Relaxed selective pressure was examined in the cetacean lineages with inactivated TRPV3, which might contribute to its exceptionally thickened stratum spinosum as the significant thickening of stratum spinosum in TRPV3 knock‐out mouse. However, functional TRPV3 may exist in several terrestrial mammals due to their strong purifying selection, although they have “inactivating mutations.” Further, for intact sequences, relaxed selective constraints on the TRPV3 gene were also detected in aquatic cetaceans, manatees, and semi‐aquatic hippopotamus. However, they had intact TRPV3, suggesting that the accumulation of inactivating mutations might have lagged behind the relaxed selective pressure. The results of this study revealed the decay of TRPV3 being the genomic trace of epidermal development in aquatic and semi‐aquatic mammals. They provided insights into convergently evolutionary changes of epidermal structures during the transition from the terrestrial to the aquatic environment.

Transitions in development - an interview with Chin-Min (Kimmy) Ho.

Kimmy Ho is an Assistant Research Fellow at the Institute of Plant and Microbial Biology, Academia Sinica, Taiwan. Her research focuses on leaf epidermal development. We caught up with Kimmy over Zoom to find out about her research, her transition to becoming a group leader and her approach to mentoring students.

RIPK4 regulates cell-cell adhesion in epidermal development and homeostasis.

Epidermal development and maintenance are finely regulated events requiring a strict balance between proliferation and differentiation. Alterations in these processes give rise to human disorders such as cancer or syndromes with skin and annexes defects, known as ectodermal dysplasias (EDs). Here, we studied the functional effects of two novel receptor-interacting protein kinase 4 (RIPK4) missense mutations identified in siblings with an autosomal recessive ED with cutaneous syndactyly, palmoplantar hyperkeratosis and orofacial synechiae. Clinical overlap with distinct EDs caused by mutations in transcription factors (i.e. p63 and interferon regulatory factor 6, IRF6) or nectin adhesion molecules was noticed. Impaired activity of the RIPK4 kinase resulted both in altered epithelial differentiation and defective cell adhesion. We showed that mutant RIPK4 resulted in loss of PVRL4/nectin-4 expression in patient epidermis and primary keratinocytes, and demonstrated that PVRL4 is transcriptionally regulated by IRF6, a RIPK4 phosphorylation target. In addition, defective RIPK4 altered desmosome morphology through modulation of plakophilin-1 and desmoplakin. In conclusion, this work implicates RIPK4 kinase function in the p63-IRF6 regulatory loop that controls the proliferation/differentiation switch and cell adhesion, with implications in ectodermal development and cancer.

HSL1 and BAM1/2 impact epidermal cell development by sensing distinct signaling peptides

The membrane receptor kinases HAESA and HSL2 recognize a family of IDA/IDL signaling peptides to control cell separation processes in different plant organs. The homologous HSL1 has been reported to regulate epidermal cell patterning by interacting with a different class of signaling peptides from the CLE family. Here we demonstrate that HSL1 binds IDA/IDL peptides with high, and CLE peptides with lower affinity, respectively. Ligand sensing capability and receptor activation of HSL1 require a SERK co-receptor kinase. Crystal structures with IDA/IDLs or with CLE9 reveal that HSL1-SERK1 complex recognizes the entire IDA/IDL signaling peptide, while only parts of CLE9 are bound to the receptor. In contrast, the receptor kinase BAM1 interacts with the entire CLE9 peptide with high affinity and specificity. Furthermore, the receptor tandem BAM1/BAM2 regulates epidermal cell division homeostasis. Consequently, HSL1-IDLs and BAM1/BAM2-CLEs independently regulate cell patterning in the leaf epidermal tissue.

ECM degradation in the Drosophila abdominal epidermis initiates tissue growth that ceases with rapid cell-cycle exit

SummaryDuring development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle.

Identification and Verification of Five Potential Biomarkers Related to Skin and Thermal Injury Using Weighted Gene Co-Expression Network Analysis.

Background: Burn injury is a life-threatening disease that does not have ideal biomarkers. Therefore, this study first applied weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) screening methods to identify pivotal genes and diagnostic biomarkers associated with the skin burn process. Methods: After obtaining transcriptomic datasets of burn patient skin and normal skin from Gene Expression Omnibus (GEO) and performing differential analysis and functional enrichment, WGCNA was used to identify hub gene modules associated with burn skin processes in the burn patient peripheral blood sample dataset and determine the correlation between modules and clinical features. Enrichment analysis was performed to identify the functions and pathways of key module genes. Differential analysis, WGCNA, protein-protein interaction analysis, and enrichment analysis were utilized to screen for hub genes. Hub genes were validated in two other GEO datasets, tested by immunohistochemistry for hub gene expression in burn patients, and receiver operating characteristic curve analysis was performed. Finally, we constructed the specific drug activity, transcription factors, and microRNA regulatory network of the five hub genes. Results: A total of 1,373 DEGs in GSE8056 were obtained, and the top 5 upregulated genes were S100A12, CXCL8, CXCL5, MMP3, and MMP1, whereas the top 5 downregulated genes were SCGB1D2, SCGB2A2, DCD, TSPAN8, and KRT25. DEGs were significantly enriched in the immunity, epidermal development, and skin development processes. In WGCNA, the yellow module was identified as the most closely associated module with tissue damage during the burn process, and the five hub genes (ANXA3, MCEMP1, MMP9, S100A12, and TCN1) were identified as the key genes for burn injury status, which consistently showed high expression in burn patient blood samples in the GSE37069 and GSE13902 datasets. Furthermore, we verified using immunohistochemistry that these five novel hub genes were also significantly elevated in burn patient skin. In addition, MCEMP1, MMP9, and S100A12 showed perfect diagnostic performance in the receiver operating characteristic analysis. Conclusion: In conclusion, we analyzed the changes in genetic processes in the skin during burns and used them to identify five potential novel diagnostic markers in blood samples from burn patients, which are important for burn patient diagnosis. In particular, MCEMP1, MMP9, and S100A12 are three key blood biomarkers that can be used to identify skin damage in burn patients.

Mechanism of tobacco osmotin gene in plant responses to biotic and abiotic stress tolerance: A brief history

Plants are recurrently exposed to myriads of biotic and abiotic stresses leading to several biochemical and physiological variations that cause severe impacts on plant growth and survival. To overcome these challenges, plants activate two primary defense mechanisms, such as structural response (cell wall strengthening and waxy epidermal cuticle development) and metabolic changes, including the synthesis of anti-microbial compounds and proteins, especially the pathogenesis-related (PR) proteins. PR proteins are members of a super large family of defense proteins that exhibit antimicrobial activities. Their over-expression in plants provides tolerance to many abiotic and biotic stresses. PR proteins have been classified into 17 families, including PR-5–also called thaumatin-like proteins (TLPs) that involve osmotin and osmotin-like proteins (OLPs). Osmotin was first identified in tobacco (Nicotiana tabacum var. Wisconsin 38), and then its homolog proteins (OLPs) were reported from the whole plant kingdom. Osmotin and OLPs are ubiquitous in all fruits and vegetables. Their expression has been detected in various plant tissues and organs. The phylogenetic tree studies revealed that the osmotin group originated from spermatophytes. Moreover, the atomic structure of OLP has shown similarity to thaumatin and TLPs from monocot and eudicot species, which determines a strong evolutionary pressure in flowering plants for conserving thaumatin fold. This is associated with the role of these proteins against pathogens as defense molecules and to induce stress tolerance to plants against several biotic and abiotic factors. In this review, we have briefly described the development history of osmotin, including its function and mechanism to induce biotic and abiotic stress tolerance to plants.