Conserved Transcription Factor Research Articles

TWIST1 Gene Variants Cause Craniosynostosis with Limb Abnormalities in Asian Patients

AbstractThe TWIST1 gene codes for a highly conserved transcription factor in a basic helix–loop–helix transcription factors family. The pattern of inheritance is autosomal dominant in Saethre–Chotzen syndrome, Robinow–Sorauf syndrome, and Sweeney–Cox syndrome. Major features of these syndromes include coronal synostosis, vision problems, and deafness, and facial features include hypertelorism, low-set ears, arched eyebrows, beaked nose, maxillary hypoplasia, and other dysmorphisms including broad great toes, clinodactyly, brachydactyly, and cutaneous syndactyly. TWIST1 (bHLH) transcription factor regulates the formation of head and limbs in the embryo. We describe three families affected with craniosynostosis in whom a sporadic TWIST1 variant was identified on whole exome sequencing, chromosomal microarray, and Sanger sequencing.

Recent Advances in Transcription Factors Biomarkers and Targeted Therapies Focusing on Epithelial–Mesenchymal Transition

Transcription factors involve many proteins in the process of transactivating or transcribing (none-) encoded DNA to initiate and regulate downstream signals, such as RNA polymerase. Their unique characteristic is that they possess specific domains that bind to specific DNA element sequences called enhancer or promoter sequences. Epithelial–mesenchymal transition (EMT) is involved in cancer progression. Many dysregulated transcription factors—such as Myc, SNAIs, Twists, and ZEBs—are key drivers of tumor metastasis through EMT regulation. This review summarizes currently available evidence related to the oncogenic role of classified transcription factors in EMT editing and epigenetic regulation, clarifying the roles of the classified conserved transcription factor family involved in the EMT and how these factors could be used as therapeutic targets in future investigations.

LncRNA MtCIR2 positively regulates plant-freezing tolerance by modulating CBF/DREB1 gene clusters.

Emerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in regulation of plant response to environmental stress. CBF/DREB1s are highly conserved transcription factors that regulate response to cold stress in plants. However, very few lncRNAs were found to regulate expression of CBFs and cold tolerance in plant. Here, we identified a cold-responsive long intergenic noncoding RNA (MtCIR2) of CBF/DREB1 genes that were located in a major freezing tolerance QTL region of legume Medicago truncatula. We found that response of MtCIR2 transcription was more rapid than that of MtCBF/DREB1s during cold treatment. MtCIR2 positively regulated M. truncatula freezing tolerance, such that overexpression of MtCIR2 led to higher survival rate and lower cell membrane damage than wild-type plants, while mutation of MtCIR2 rendered the mutants more sensitive to cold stress. In addition, expression levels of MtCBF/DREB1s were up-regulated in the MtCIR2 overexpressing lines and down-regulated in the mutants. Among the MtCIR2-regulated genes, the strongest enriched genes were those involved in polysaccharide metabolic processes. In addition, we demonstrated that overexpression of MtCIR2 led to increases in contents of soluble sugars. These results highlight that MtCIR2 positively regulates tolerance to freezing by regulating MtCBF/DREB1s expression and glycometabolism in M. truncatula.

A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes.

Recent large-scale genomic association studies found evidence for a genetic link between increased risk of type 2 diabetes and decreased risk for adiposity-related traits, reminiscent of metabolically obese normal weight (MONW) association signatures. However, the target genes and cellular mechanisms driving such MONW associations remain to be identified. Here, we systematically identify the cellular programmes of one of the top-scoring MONW risk loci, the 2q24.3 risk locus, in subcutaneous adipocytes. We identify a causal genetic variant, rs6712203, an intronic single-nucleotide polymorphism in the COBLL1 gene, which changes the conserved transcription factor motif of POU domain, class 2, transcription factor 2, and leads to differential COBLL1 gene expression by altering the enhancer activity at the locus in subcutaneous adipocytes. We then establish the cellular programme under the genetic control of the 2q24.3 MONW risk locus and the effector gene COBLL1, which is characterized by impaired actin cytoskeleton remodelling in differentiating subcutaneous adipocytes and subsequent failure of these cells to accumulate lipids and develop into metabolically active and insulin-sensitive adipocytes. Finally, we show that perturbations of the effector gene Cobll1 in a mouse model result in organismal phenotypes matching the MONW association signature, including decreased subcutaneous body fat mass and body weight along with impaired glucose tolerance. Taken together, our results provide a mechanistic link between the genetic risk for insulin resistance and low adiposity, providing a potential therapeutic hypothesis and a framework for future identification of causal relationships between genome associations and cellular programmes in other disorders.

The people behind the papers - Zainab Afzal and Robb Krumlauf.

Hox genes encode a family of conserved transcription factors that play important roles in specifying regions of the body plan along the anterior-posterior axis. A new paper in Development introduces new approaches and provides further insights into the transcriptional mechanisms controlling Hox gene expression during vertebrate development. To hear more about the story behind the paper, we caught up with the first author Zainab Afzal and her PhD supervisor Robb Krumlauf, Professor at the Stowers Institute for Medical Research.

The MADS-box gene EjAGL15 positively regulates lignin deposition in the flesh of loquat fruit during its storage.

Lignification of fruit flesh is a common physiological disorder that occurs during post-harvest storage, resulting in the deterioration of fruit quality. Lignin deposition in loquat fruit flesh occurs due to chilling injury or senescence, at temperatures around 0°C or 20°C, respectively. Despite extensive research on the molecular mechanisms underlying chilling-induced lignification, the key genes responsible for the lignification process during senescence in loquat fruit remain unknown. MADS-box genes, an evolutionarily conserved transcription factor family, have been suggested to play a role in regulating senescence. However, it is still unclear whether MADS-box genes can regulate the lignin deposition that arises from fruit senescence. Both senescence- and chilling-induced flesh lignification were simulated by applying temperature treatments on loquat fruits. The flesh lignin content during the storage was measured. Transcriptomic, quantitative reverse transcription PCR and correlation analysis were employed to identify key MADS-box genes that may be involved in flesh lignification. The Dual-luciferase assay was utilized to identify the potential interactions between MADS-box members and genes in phenylpropanoid pathway. The lignin content of the flesh samples treated at 20°C or 0°C increased during storage, but at different rates. Results from transcriptome analysis, quantitative reverse transcription PCR, and correlation analysis led us to identify a senescence-specific MADS-box gene, EjAGL15, which correlated positively with the variation in lignin content of loquat fruit. Luciferase assay results confirmed that EjAGL15 activated multiple lignin biosynthesis-related genes. Our findings suggest that EjAGL15 functions as a positive regulator of senescence-induced flesh lignification in loquat fruit.

Role of bZIP Transcription Factors in Plant Salt Stress.

Soil salinity has become an increasingly serious problem worldwide, greatly limiting crop development and yield, and posing a major challenge to plant breeding. Basic leucine zipper (bZIP) transcription factors are the most widely distributed and conserved transcription factors and are the main regulators controlling various plant response processes against external stimuli. The bZIP protein contains two domains: a highly conserved, DNA-binding alkaline region, and a diverse leucine zipper, which is one of the largest transcription factor families in plants. Plant bZIP is involved in many biological processes, such as flower development, seed maturation, dormancy, and senescence, and plays an important role in abiotic stresses such as salt damage, drought, cold damage, osmotic stress, mechanical damage, and ABA signal response. In addition, bZIP is involved in the regulation of plant response to biological stresses such as insect pests and pathogen infection through salicylic acid, jasmonic acid, and ABA signal transduction pathways. This review summarizes and discusses the structural characteristics and functional characterization of the bZIP transcription factor group, the bZIP transcription factor complex and its molecular regulation mechanisms related to salt stress resistance, and the regulation of transcription factors in plant salt stress resistance. This review provides a theoretical basis and research ideas for further exploration of the salt stress-related functions of bZIP transcription factors. It also provides a theoretical basis for crop genetic improvement and green production in agriculture.

Distribution of the transcription factor islet-1 in the central nervous system of nonteleost actinopterygian fish: Relationship with cholinergic and catecholaminergic systems.

Islet-1 (Isl1) is one of the most conserved transcription factors in the evolution of vertebrates, due to its continuing involvement in such important functions as the differentiation of motoneurons, among other essential roles in cell fate in the forebrain. Although its functions are thought to be similar in all vertebrates, the knowledge about the conservation of its expression pattern in the central nervous system goes as far as teleosts, leaving the basal groups of actinopterygian fishes overlooked, despite their important phylogenetic position. In order to assess the extent of its conservation among vertebrates, we studied its expression pattern in the central nervous system of selected nonteleost actinopterygian fishes. By means of immunohistochemical techniques, we analyzed the Isl1 expression in the brain, spinal cord, and sensory ganglia of the cranial nerves of young adult specimens of the cladistian species Polypterus senegalus and Erpetoichthys calabaricus, the chondrostean Acipenser ruthenus, and the holostean Lepisosteus oculatus. We also detected the presence of the transcription factor Orthopedia and the enzymes tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) to better locate all the immunoreactive structures in the different brain areas and to reveal the possible coexpression with Isl1. Numerous conserved features in the expression pattern of Isl1 were observed in these groups of fishes, such as populations of cells in the subpallial nuclei, preoptic area, subparaventricular and tuberal hypothalamic regions, prethalamus, epiphysis, cranial motor nuclei and sensory ganglia of the cranial nerves, and the ventral horn of the spinal cord. Double labeling of TH and Isl1 was observed in cells of the preoptic area, the subparaventricular and tuberal hypothalamic regions, and the prethalamus, while virtually all motoneurons in the hindbrain and the spinal cord coexpressed ChAT and Isl1. Altogether, these results show the high degree of conservation of the expression pattern of the transcription factor Isl1, not only among fish, but in the subsequent evolution of vertebrates.

Genome-Wide Identification and Expression Analysis of CAMTA Gene Family Implies PbrCAMTA2 Involved in Fruit Softening in Pear

CAMTA are calcium-modulating binding transcription factors that contribute to plant development. We identified 46 CAMTA genes from eight Rosaceae species and divided them into five subgroups based on a phylogenetic tree. Our analysis indicated that CAMTA is a highly conserved family among Rosaceae species, with a conserved DNA-binding domain (CG-1) and a conserved transcription factor immunoglobulin domain (TIG). Following a recent whole-genome duplication event, the genomes of Chinese white pear, European pear, and apple experienced significant expansion, resulting in the number of CAMTA genes being twice that of the other species. Cis-element identification showed that the distribution of the zein metabolism regulation-responsive element was different in the promoters of Chinese white pear (55.56%) and European pear (11.11%) CAMTA gene families. The gene expression results showed that PbrCAMTA1, 2, 6, 7 was highly expressed in pear fruit. Among them, PbrCAMTA2 may have a key influence on fruit softening, as observed in transient transformation experiments. In conclusion, our results provide crucial insights into the evolution of the CAMTA gene family in pear and other Rosaceae species and identify a candidate PbrCAMTA gene, which is involved in the dynamic development of pear fruits.

Abstract 1499: HOXC6 gene functions as an oncogenic driver in HPV+ head and neck squamous cell carcinoma (HNSCC)

Abstract Homeobox C6 (HOXC6) belongs to the member of the homeobox family, a highly conserved transcription factor that plays an essential role in morphogenesis and cellular differentiation during embryonic development. Previous studies reported that the dysregulation of HOXC6 gene expression plays a crucial role in carcinogenesis. HOXC6 is reportedly over-expressed in several types of human cancer, including breast, leukemia, and lung cancers. Moreover, higher expression of HOXC6 leads to lymph node metastasis. In addition, it has been also demonstrated that in prostate cancer cells, HOXC6 downregulation reduced cell proliferation by inducing apoptosis. Although the precise mechanisms of HOXC6 in carcinogenesis still need to be investigated. In a secondary data analysis from our previous study, we identified HOXC6 is upregulated and enriched with tumor type-specific enhancer region in HPV+HNSCC samples. Moreover, we used publicly available TCGA data consisting of 520 HNSCC samples and a JHU cohort with 47 HPV+ HNSCC samples to illustrate that HOXC6 is more highly expressed in HPV+ HNSCC than in adjacent normal samples. We further validated the HOXC6 overexpression through an in vitro study using HPV+HNSCC cell lines and patient tissue samples. Clinicopathological data from TCGA indicated that higher HOXC6 expression correlated with poor overall survival. To explore the function of HOXC6 in HNSCC, we knocked down HOXC6 in HPV+ HNSCC cells via siRNA and performed the cell proliferation assay. We observed that HOXC6 downregulation decreased the cell proliferation rate compared to control samples. In conclusion, our results suggest HOXC6 acts as an oncogenic driver in HPV+ HNSCC progression, which is potentially regulated by tumor type-specific enhancers and may serve as a potential biomarker. Citation Format: Subhendu Roy Choudhury, Vera Mukhina, Iuliia Vyshkvorkina, Jessica Gore, Alexa Anderson, Daria A. Gaykalova. HOXC6 gene functions as an oncogenic driver in HPV+ head and neck squamous cell carcinoma (HNSCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1499.

Conserved transcription factors promote cell fate stability and restrict reprogramming potential in differentiated cells

Defining the mechanisms safeguarding cell fate identity in differentiated cells is crucial to improve 1) - our understanding of how differentiation is maintained in healthy tissues or altered in a disease state, and 2) - our ability to use cell fate reprogramming for regenerative purposes. Here, using a genome-wide transcription factor screen followed by validation steps in a variety of reprogramming assays (cardiac, neural and iPSC in fibroblasts and endothelial cells), we identified a set of four transcription factors (ATF7IP, JUNB, SP7, and ZNF207 [AJSZ]) that robustly opposes cell fate reprogramming in both lineage and cell type independent manners. Mechanistically, our integrated multi-omics approach (ChIP, ATAC and RNA-seq) revealed that AJSZ oppose cell fate reprogramming by 1) - maintaining chromatin enriched for reprogramming TF motifs in a closed state and 2) - downregulating genes required for reprogramming. Finally, KD of AJSZ in combination with MGT overexpression, significantly reduced scar size and improved heart function by 50%, as compared to MGT alone post-myocardial infarction. Collectively, our study suggests that inhibition of barrier to reprogramming mechanisms represents a promising therapeutic avenue to improve adult organ function post-injury.

NHA1 is a cation/proton antiporter essential for the water-conserving functions of the rectal complex in Tribolium castaneum

More than half of all extant metazoan species on earth are insects. The evolutionary success of insects is linked with their ability to osmoregulate, suggesting that they have evolved unique physiological mechanisms to maintain water balance. In beetles (Coleoptera)-the largest group of insects-a specialized rectal ("cryptonephridial") complex has evolved that recovers water from the rectum destined for excretion and recycles it back to the body. However, the molecular mechanisms underpinning the remarkable water-conserving functions of this system are unknown. Here, we introduce a transcriptomic resource, BeetleAtlas.org, for the exceptionally desiccation-tolerant red flour beetleTribolium castaneum,and demonstrate its utility by identifying a cation/H+antiporter (NHA1) that is enriched and functionally significant in theTriboliumrectal complex. NHA1 localizes exclusively to a specialized cell type, the leptophragmata, in the distal region of the Malpighian tubules associated with the rectal complex. Computational modeling and electrophysiological characterization inXenopus oocytesshow that NHA1 acts as an electroneutral K+/H+antiporter. Furthermore, genetic silencing ofNha1dramatically increases excretory water loss and reduces organismal survival during desiccation stress, implying that NHA1 activity is essential for maintaining systemic water balance. Finally, we show that Tiptop, a conserved transcription factor, regulates NHA1 expression in leptophragmata and controls leptophragmata maturation, illuminating the developmental mechanism that establishes the functions of this cell. Together, our work providesinsights into the molecular architecture underpinning the function of one of the most powerful water-conserving mechanisms in nature,the beetle rectal complex.

Global analysis of basic leucine zipper transcription factors in trifoliate orange and the function identification of PtbZIP49 in salt tolerance

As one of the most widely distributed and highly conserved transcription factors in eukaryotes, basic leucine zipper proteins (bZIPs) are involved in a variety of biological processes in plants, but they are largely unknown in citrus. In this study, 56 bZIP family members were identified genome-wide from an important citrus rootstock, namely trifoliate orange (Poncirus trifoliata L. Raf.), and these putative bZIPs were named PtbZIP1–PtbZIP56. All PtbZIPs were classified into 13 subgroups by phylogenetic comparison with Arabidopsis thaliana bZIPs (AtbZIPs), and they were randomly distributed on nine known (50 genes) chromosomes and one unknown (6 genes) chromosome. Sequence analysis revealed the detailed characteristics of PtPZIPs, including their amino acid length, isoelectric point (pI), molecular weight (MW), predicted subcellular localization, gene structure, and conserved motifs. Prediction of promoter elements suggested the presence of drought, low-temperature, wound, and defense and stress responsive elements, as well as multiple hormone-responsive cis-acting elements. Spatiotemporal expression analysis showed the transcriptional patterns of PtbZIPs in different tissues and under dehydration, high salt, ABA, and IAA treatments. In addition, 21 PtbZIPs were predicted to have direct or indirect protein–protein interactions. Among these, PtbZIP49 was experimentally proven to interact with PtbZIP1 or PtbZIP11 by using a yeast two-hybrid assay and bimolecular fluorescence complementation (BiFC). Subcellular localization analysis further revealed that PtbZIP1, PtbZIP11, and PtbZIP49 were localized in the nucleus. Moreover, PtbZIP49 was functionally identified as having an important role in salt stress via ectopic expression in A. thaliana and silenced in trifoliate orange using virus-induced gene silencing (VIGS). This study provided comprehensive information on PtbZIP transcription factors in citrus and highlights their potential functions in abiotic stress.

Retinoic Acid and POU Genes in Developing Amphioxus: A Focus on Neural Development.

POU genes are a family of evolutionarily conserved transcription factors with key functions in cell type specification and neurogenesis. In vitro experiments have indicated that the expression of some POU genes is controlled by the intercellular signaling molecule retinoic acid (RA). In this work, we aimed to characterize the roles of RA signaling in the regulation of POU genes in vivo. To do so, we studied POU genes during the development of the cephalochordate amphioxus, an animal model crucial for understanding the evolutionary origins of vertebrates. The expression patterns of amphioxus POU genes were assessed at different developmental stages by chromogenic in situ hybridization and hybridization chain reaction. Expression was further assessed in embryos subjected to pharmacological manipulation of endogenous RA signaling activity. In addition to a detailed description of the effects of these treatments on amphioxus POU gene expression, our survey included the first description of Pou2 and Pou6 expression in amphioxus embryos. We found that Pit-1, Pou2, Pou3l, and Pou6 expression are not affected by alterations of endogenous RA signaling levels. In contrast, our experiments indicated that Brn1/2/4 and Pou4 expression are regulated by RA signaling in the endoderm and the nerve cord, respectively. The effects of the treatments on Pou4 expression in the nerve cord revealed that, in developing amphioxus, RA signaling plays a dual role by (1) providing anteroposterior patterning information to neural cells and (2) specifying neural cell types. This finding is coherent with a terminal selector function of Pou4 for GABAergic neurons in amphioxus and represents the first description of RA-induced changes in POU gene expression in vivo.

Species-specific transcriptional reprogramming during adventitious root initiation.

Adventitious roots or shoot-borne roots transdifferentiate from cells close to vascular tissues after cell reprogramming, which is associated with increased transcriptional activity. Recently, Garg et al. provided a genome-wide landscape of transcriptional signatures during the early stages of adventitious root initiation in rice and showed that conserved transcription factors acquire species-specific function.

Pneumococcal capsule expression is controlled through a conserved, distal cis-regulatory element during infection.

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial pneumonia in the US and worldwide. Studies have shown that the differing chemical make-up between serotypes of its most important virulence factor, the capsule, can dictate disease severity. Here we demonstrate that control of capsule synthesis is also critical for infection and facilitated by two broadly conserved transcription factors, SpxR and CpsR, through a distal cis-regulatory element we name the 37-CE. Strikingly, changing only three nucleotides within this sequence is sufficient to render pneumococcus avirulent. Using in vivo and in vitro approaches, we present a model where SpxR interacts as a unique trimeric quaternary structure with the 37-CE to enable capsule repression in the airways. Considering its dramatic effect on infection, variation of the 37-CE between serotypes suggests this molecular switch could be a critical contributing factor to this pathogen's serotype-specific disease outcomes.

A transcriptional activator from Rhizophagus irregularis regulates phosphate uptake and homeostasis in AM symbiosis during phosphorous starvation.

Phosphorus (P) is one of the most important nutrient elements for plant growth and development. Under P starvation, arbuscular mycorrhizal (AM) fungi can promote phosphate (Pi) uptake and homeostasis within host plants. However, the underlying mechanisms by which AM fungal symbiont regulates the AM symbiotic Pi acquisition from soil under P starvation are largely unknown. Here, we identify a HLH domain containing transcription factor RiPho4 from Rhizophagus irregularis. To investigate the biological functions of the RiPho4, we combined the subcellular localization and Yeast One-Hybrid (Y1H) experiments in yeasts with gene expression and virus-induced gene silencing approach during AM symbiosis. The approach during AM symbiosis. The results indicated that RiPho4 encodes a conserved transcription factor among different fungi and is induced during the in planta phase. The transcription of RiPho4 is significantly up-regulated by P starvation. The subcellular localization analysis revealed that RiPho4 is located in the nuclei of yeast cells during P starvation. Moreover, knock-down of RiPho4 inhibits the arbuscule development and mycorrhizal Pi uptake under low Pi conditions. Importantly, RiPho4 can positively regulate the downstream components of the phosphate (PHO) pathway in R. irregularis. In summary, these new findings reveal that RiPho4 acts as a transcriptional activator in AM fungus to maintain arbuscule development and regulate Pi uptake and homeostasis in the AM symbiosis during Pi starvation.

Segmentation, 3D Reconstruction, and Analysis of PcG Proteins in Fluorescence Microscopy Images in Different Cell Culture Conditions.

Polycomb-group (PcG) of proteins are evolutionarily conserved transcription factors necessary for the regulation of gene expression during the development and the safeguard of cell identity in adulthood. In the nucleus, they form aggregates whose positioning and dimension are fundamental for their function. We present an algorithm, and its MATLAB implementation, based on mathematical methods to detect and analyze PcG proteins in fluorescence cell image z-stacks. Our algorithm provides a method to measure the number, the size, and the relative positioning of the PcG bodies in the nucleus for a better understanding of their spatial distribution, and thus of their role for a correct genome conformation and function.

Hox genes in development and beyond.

Hox genes encode evolutionarily conserved transcription factors that are essential for the proper development of bilaterian organisms. Hox genes are unique because they are spatially and temporally regulated during development in a manner that is dictated by their tightly linked genomic organization. Although their genetic function during embryonic development has been interrogated, less is known about how these transcription factors regulate downstream genes to direct morphogenetic events. Moreover, the continued expression and function of Hox genes at postnatal and adult stages highlights crucial roles for these genes throughout the life of an organism. Here, we provide an overview of Hox genes, highlighting their evolutionary history, their unique genomic organization and how this impacts the regulation of their expression, what is known about their protein structure, and their deployment in development and beyond.

Identification of Bottle Gourd (Lagenaria siceraria) OVATE Family Genes and Functional Characterization of LsOVATE1.

The OVATE gene family is a class of conserved transcription factors that play significant roles in plant growth, development, and abiotic stress, and also affect fruit shape in vegetable crops. Bottle gourd (Lagenaria siceraria), commonly known as calabash or gourd, is an annual climber belonging to the Cucurbitaceae family. Studies on bottle gourd OVATE genes are limited. In this study, we performed genome-wide identification of the OVATE gene family in bottle gourd, and identified a total of 20 OVATE family genes. The identified genes were unevenly distributed across 11 bottle gourd chromosomes. We also analyzed the gene homology, amino acid sequence conservation, and three-dimensional protein structure (via prediction) of the 20 OVATE family genes. We used RNA-seq data to perform expression analysis, which found 20 OVATE family genes to be differentially expressed based on spatial and temporal characteristics, suggesting that they have varying functions in the growth and development of bottle gourd. In situ hybridization and subcellular localization analysis showed that the expression characteristics of the LsOVATE1 gene, located on chromosome 7 homologous to OVATE, is a candidate gene for affecting the fruit shape of bottle gourd. In addition, RT-qPCR data from bottle gourd roots, stems, leaves, and flowers showed different spatial expression of the LsOVATE1 gene. The ectopic expression of LsOVATE1 in tomato generated a phenotype with a distinct fruit shape and development. Transgenic-positive plants that overexpressed LsOVATE1 had cone-shaped fruit, calyx hypertrophy, petal degeneration, and petal retention after flowering. Our results indicate that LsOVATE1 could serve important roles in bottle gourd development and fruit shape determination, and provide a basis for future research into the function of LsOVATE1.