{"title":"fos genes in mainly invertebrate model systems: A review of commonalities and some diversities","authors":"Manuel Zúniga-García , Juan Rafael Riesgo-Escovar","doi":"10.1016/j.cdev.2025.203997","DOIUrl":"10.1016/j.cdev.2025.203997","url":null,"abstract":"<div><div><em>fos</em> genes, transcription factors with a common basic region and leucine zipper domains binding to a consensus DNA sequence (TGA{}TCA), are evolutionarily conserved in eukaryotes. Homologs can be found in many different species from yeast to vertebrates. In yeast, the homologous <em>GCN4</em> gene is required to mediate “emergency” situations like nutrient deprivation and the unfolded protein response. The <em>C. elegans</em> homolog <em>fos-1</em> is required for reproduction and vulval development, as well as in adult homeostasis. In <em>Drosophila melanogaster</em>, there is also a sole <em>fos</em> homolog: the gene <em>kayak</em>, with five isoforms<em>.</em> The <em>kayak</em> locus has been studied in detail. It was originally described as embryonic lethal with a “dorsal open” phenotype. Since then, <em>kayak</em> has been shown to be required for oocyte maturation and as a source for piRNA; for early dorsoventral specification, macrophage function, dorsal closure, endoderm differentiation, and finally during metamorphosis in wing and eye-antennal development. In mammals there are multiple <em>fos</em> loci, each one with alternative splicing giving rise to multiple isoforms. Overall, mammalian <em>fos</em> genes are required for bone, cartilage and tooth formation, and in some instances for placental angiogenesis and retinal function. We review here mainly what is known about <em>fos</em> function in invertebrate model systems, especially during embryogenesis. We propose that <em>fos</em> genes, evolutionarily conserved transcription factors, evolved early during eukaryotic development, and from its inception as part of an environmental stress response machinery, were co-opted several times during development to regulate processes that may require similar cellular responses.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203997"},"PeriodicalIF":3.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yasir Suhail , Yamin Liu , Junaid Afzal , Wenqiang Du , Paul Robson , Ashkan Novin , Ramalakshmi Ramasamy , Kshitiz
{"title":"Extravillous trophoblasts reverse the decidualization induced increase in matrix production by secreting TGFβ antagonists Emilin-1 and Gremlin-1","authors":"Yasir Suhail , Yamin Liu , Junaid Afzal , Wenqiang Du , Paul Robson , Ashkan Novin , Ramalakshmi Ramasamy , Kshitiz","doi":"10.1016/j.cdev.2025.203994","DOIUrl":"10.1016/j.cdev.2025.203994","url":null,"abstract":"<div><div>The maternal-fetal interface has long been considered as a frontier for an evolutionary arms race due to the close juxtaposition of genetically distinct tissues. In hemochorial species with deep placental invasion, including in humans, maternal stroma prepares its defenses against deep trophoblast invasion by decidualization, a differentiation process characterized by increased stromal cell matrix production, and contractile force generation. Decidualization has evolved from an ancestral wound healing response of fibroblast activation by the endometrial stroma. On the placental side, a new trophoblast cell type in great apes has recently evolved, called extravillous trophoblast (EVT), with an exceptionally high invasive capability. Using HTR8, and differentiated EVTs from trophectodermal stem cells, we show that EVTs partly counter decidual myofibroblast activation derived defenses. This reversal in decidual defenses is achieved by secreted antagonists of Transforming Growth Factor β/Bone morphogenic pathway, specifically Emilin-1 and Gremlin-1. Emilin-1 and Gremlin-1 reverse TGFβ activation in decidual cells, reducing high collagen production, and expression of genes associated with myofibroblast transformation. We also show that these secreted TGFβ antagonists can functionally reverse acquired decidual resistance to trophoblast invasion. As our work highlights new mechanisms evolved by trophoblasts to regulate stromal invasibility, it has broader implications in other invasive processes, including wound healing, and cancer metastasis.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203994"},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Schwann cells have a limited window of time in which to initiate myelination signaling during early migration in vivo","authors":"Océane El-Hage , Aya Mikdache , Marie-José Boueid , Cindy Degerny , Marcel Tawk","doi":"10.1016/j.cdev.2024.203993","DOIUrl":"10.1016/j.cdev.2024.203993","url":null,"abstract":"<div><div>The temporal control of mitotic exit of individual Schwann cells (SCs) is essential for radial sorting and peripheral myelination. However, it remains unknown when, during their multiple rounds of division, SCs initiate myelin signaling <em>in vivo</em>. By manipulating SC division during development, we report that when SCs skip their division during migration, but not during radial sorting, they fail to myelinate peripheral axons. This coincides with a sharp decrease in Laminin expression within the posterior lateral line nerve. Interestingly, elevating cAMP levels or forcing Laminin 2 expression within individual SCs restore their ability to myelinate, despite missing mitosis during migration. Our results demonstrate a limited time window during which migrating SCs initiate Laminin expression to gradually activate the Laminin/Gpr126/cAMP signaling required for radial sorting and myelination at later stages <em>in vivo</em>.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203993"},"PeriodicalIF":3.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucia Leitner , Martina Schultheis , Franziska Hofstetter , Claudia Rudolf , Christiane Fuchs , Valeria Kizner , Kerstin Fiedler , Marie-Therese Konrad , Julia Höbaus , Marco Genini , Julia Kober , Elisabeth Ableitner , Teresa Gmaschitz , Diana Walder , Georg Weitzer
{"title":"An autocrine synergistic desmin-SPARC network promotes cardiomyogenesis in cardiac stem cells","authors":"Lucia Leitner , Martina Schultheis , Franziska Hofstetter , Claudia Rudolf , Christiane Fuchs , Valeria Kizner , Kerstin Fiedler , Marie-Therese Konrad , Julia Höbaus , Marco Genini , Julia Kober , Elisabeth Ableitner , Teresa Gmaschitz , Diana Walder , Georg Weitzer","doi":"10.1016/j.cdev.2024.203990","DOIUrl":"10.1016/j.cdev.2024.203990","url":null,"abstract":"<div><div>The mammalian heart contains cardiac stem cells throughout life, but it has not been possible to harness or stimulate these cells to repair damaged myocardium in vivo. Assuming physiological relevance of these cells, which have evolved and have been maintained throughout mammalian evolution, we hypothesize that cardiac stem cells may contribute to cardiomyogenesis in an unorthodox manner. Since the intermediate filament protein desmin and the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) promote cardiomyogenic differentiation during embryogenesis in a cell-autonomous and paracrine manner, respectively, we focus on their genes and employ mouse embryonic and cardiac stem cell lines as in vitro models to ask whether desmin and SPARC cooperatively influence cardiomyogenesis in cardiac stem and progenitor cells. We show that desmin also promotes cardiomyogenesis in a non-cell autonomous manner by increasing the expression and secretion of SPARC in differentiating embryonic stem cells. SPARC is also secreted by cardiac stem cells where it promotes cardiomyogenesis in an autocrine and concentration-dependent manner by upregulating the expression of myocardial transcription factors and its elicitor desmin. Desmin and SPARC interact genetically, forming a positive feedback loop and secreted autocrine and paracrine SPARC negatively affects sparc mRNA expression. Paracrine SPARC rescues cardiomyogenic desmin-haploinsufficiency in cardiac stem cells in a glycosylation-dependent manner, increases desmin expression, the phosphorylation of Smad2 and induces the expression of <em>gata4, nkx2.5</em> and <em>mef2C</em>. Demonstration that desmin-induced autocrine secretion of SPARC in cardiac stem cells promotes cardiomyogenesis raises the possibility that a physiological function of cardiac stem cells in the adult and aging heart may be the gland-like secretion of factors such as SPARC that modulate age-related and adverse environmental influences and thereby contribute to cardiac homeostasis throughout life.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"181 ","pages":"Article 203990"},"PeriodicalIF":3.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Ying Cheok , Grace Min Yi Tan , Yee Teng Chan , Suhailah Abdullah , Chung Yeng Looi , Won Fen Wong
{"title":"Podoplanin and its multifaceted roles in mammalian developmental program","authors":"Yi Ying Cheok , Grace Min Yi Tan , Yee Teng Chan , Suhailah Abdullah , Chung Yeng Looi , Won Fen Wong","doi":"10.1016/j.cdev.2024.203943","DOIUrl":"10.1016/j.cdev.2024.203943","url":null,"abstract":"<div><div>Podoplanin is a vital molecule which plays an integral part in the regulation of development, immunity, and cancer. Expression of Podoplanin is detected at different early developmental stages of mammalian embryo, and it functions to modulate morphogenesis of various organ systems. In experimental animal models of different genetic backgrounds, absence of Podoplanin results in either embryonic lethality or immediate death upon birth, suggesting the importance of the gene in early developmental processes. This review discusses the gene and protein structure of Podoplanin; and elucidates various functions of Podoplanin in different systems, including central nervous system as well as respiratory, lymphatic, and cardiovascular systems.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203943"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Of criminals and cancer: The importance of social bonds and innate morality on cellular societies","authors":"Anuraag Bukkuri , Frederick R. Adler","doi":"10.1016/j.cdev.2024.203964","DOIUrl":"10.1016/j.cdev.2024.203964","url":null,"abstract":"<div><div>The current dogma in cancer biology contends that cancer is an identity problem: mutations in a cell's DNA cause it to “go rogue” and proliferate out of control. However, this largely ignores the role of cell-cell interaction and fails to explain phenomena such as cancer reversion, the existence of cancers without mutations, and foreign-body carcinogenesis. In this proof-of-concept paper, we draw on criminology to propose that cancer may alternatively be conceptualized as a relational problem: Although a cell's genetics is essential, the influence of its interaction with other cells is equally important in determining its phenotype. We create a simple agent-based network model of interactions among normal and cancer cells to demonstrate this idea. We find that both high mutation rates and low levels of connectivity among cells can promote oncogenesis. Viewing cancer as a breakdown in communication networks among cells in a tissue complements the gene-centric paradigm nicely and provides a novel perspective for understanding and treating cancer.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203964"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinlei Liu , Sijie Xie , Xiaoxue Jiang , Shuting Song, Liyan Wang, Shujie Li, Dongdong Lu
{"title":"LUC7L2 accelerates the growth of liver cancer cells by enhancing DNA damage repair via RRAS","authors":"Xinlei Liu , Sijie Xie , Xiaoxue Jiang , Shuting Song, Liyan Wang, Shujie Li, Dongdong Lu","doi":"10.1016/j.cdev.2024.203976","DOIUrl":"10.1016/j.cdev.2024.203976","url":null,"abstract":"<div><h3>Background & objectives</h3><div>LUC7L2 may be involved in the recognition of non-consensus splice donor sites in association with the U1 snRNP spliceosomal subunit. However, their detailed features and regulatory mechanisms of LUC7L2 in the development of human liver cancer have not been well characterized.</div></div><div><h3>Results</h3><div>Herein, our results demonstrate that LUC7L2 promotes the proliferation of liver cancer cells <em>in vitro and</em> xenograft transplantation <em>in vivo.</em> The proliferation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (24th hour: <em>P</em> = 0.00043; 48th hour: <em>P</em> = 0.000017). The cellular colony formation ability was significantly increased in the rLV-LUC7L2 group compared to rLV group (25.18±6.94 % <em>vs</em> 67.63±9.57 %, <em>P</em> = 0.00009). The weight of transplanted tumors was significantly increased in the rLV-LUC7L2 group compared to rLV group (0.387±0.074 <em>vs</em> 0.958± 0.103 g, <em>P</em> = 0.00004). Moreover, LUC7L2 effects on epigenetic regulation based on H3K4me3 in human liver cancer cells. e,g, RRAS. Furthermore, LUC7L2 affects transcriptome and proteome in liver cancer. In particular, LUC7L2 enhances the modification ability of H3K4me3and RNAPolII on the promoter region of RRAS and then enhances the expression of RRAS in liver cancer. Strikingly, LUC7L2 increases the increases the DNA damage repair ability dependent on RRAS. Although the DNA damage repair ability was significantly increased in the rLV-LUC7L2 group compared to rLV group(1.868±0.181 <em>vs</em> 0.17±0.034, <em>P</em> = 0.0000022), it was not significantly changed in rLV-LUC7L2+rLV-shRNA RRAS group compared with rLV group(1.868±0.181 <em>vs</em> 1.798±0.313, <em>P</em> = 0.317). Importantly, LUC7L2 enhances the carcinogenic function dependent on RRAS. In particular, RRAS increased the DNA damage repair ability by enhancing the formation of DNA damage repair dependent on tri-methylation of histone H3 lysine 36 (H3K36me3).</div></div><div><h3>Conclusions</h3><div>It is implied that LUC7L2's role in liver cancer proliferation is largely dependent on RRAS. The first discovery provides a basis for the prevention and treatment of human liver cancer.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203976"},"PeriodicalIF":3.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blastoid: The future of human development in the laboratory","authors":"Hyung Kyu Choi, Sung-Hwan Moon","doi":"10.1016/j.cdev.2024.203975","DOIUrl":"10.1016/j.cdev.2024.203975","url":null,"abstract":"<div><div>Research on early human development is crucial for understanding the origins of life and mechanisms underlying disease onset. However, these studies have significant challenges owing to ethical restrictions and technical limitations. Stem cell technology advancement has led to the development of blastoids to overcome these challenges.” Blastoids are three-dimensional structures produced by pluripotent stem cells (PSCs) that resemble the blastocyst stage of human embryos. Research on blastoids can enhance our understanding of early human development and drive innovations in regenerative medicine and disease modeling.</div><div>This review outlines the background of blastoid development and highlights the limitations of existing organoid research. It presents developments in blastoid research, from previous studies using animal models to the latest developments using human stem cell-derived blastoids in early human development studies. Additionally, this review provides a comparative analysis of the methods used to develop blastoids across various studies, evaluating their potential as ethical alternatives for regenerative medicine, human developmental biology, and embryonic research. It further assesses the ethical and social considerations surrounding blastoid research, the current strategies to address these concerns, and the potential long-term impact on science and medicine.</div><div>We aimed to provide a comprehensive understanding of the current trends in blastoid research, offer new insights into early human development, and suggest novel directions and approaches for researchers.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203975"},"PeriodicalIF":3.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging therapeutic strategies for Wnt-dependent colon cancer targeting macropinocytosis","authors":"Nydia Tejeda-Muñoz , Grace Binder , Kuo-Ching Mei","doi":"10.1016/j.cdev.2024.203974","DOIUrl":"10.1016/j.cdev.2024.203974","url":null,"abstract":"<div><div>Aberrations in the Wnt signaling pathway, particularly mutations in genes like APC and β-catenin, are pivotal in initiating and driving the progression of colorectal cancer (CRC), establishing this pathway as a crucial target for therapeutic intervention. Membrane trafficking plays a key role in regulating Wnt signaling by controlling the activation, modulation, and secretion of essential signaling molecules that contribute to CRC progression. This review explores the connection between membrane trafficking and Wnt signaling, with a specific focus on macropinocytosis—an endocytic process involved in nutrient uptake that also plays a role in Wnt signal regulation. The relationship between Wnt signaling and macropinocytosis, critical in both embryonic development and cancer onset, reveals a new dimension for therapeutic intervention. Targeting Wnt signaling through the modulation of macropinocytosis and broader membrane trafficking pathways presents a promising therapeutic strategy, with several candidates already in early clinical trials. These emerging approaches underscore the potential of targeting Wnt and its associated membrane trafficking processes for CRC treatment, aligning with the development of innovative therapies.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203974"},"PeriodicalIF":3.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The evolutionary and mechanical principles shaping the Drosophila embryonic ventral nerve cord","authors":"Katerina Karkali, Enrique Martín-Blanco","doi":"10.1016/j.cdev.2024.203973","DOIUrl":"10.1016/j.cdev.2024.203973","url":null,"abstract":"<div><div>The establishment of communication circuits requires bringing sources and targets into contact, either directly or indirectly. The Central Nervous System (CNS)'s ability to interpret the environment and generate precise responses depends on the functional efficiency of its neural network, which in turn relies on the 3D spatial organization of its constituents, mainly neurons and glia. Throughout evolution, sensory integration and motor response coordination became linked with the merging of the brain and nerve cord (NC) in the urbilaterian CNS. In most arthropods, the NC follows a specific topological plan and consists of a fixed number of neuromeres (thoracic and abdominal ganglia with commissural interconnections and a single terminal ganglion). The number, spacing, and fusion of neuromeres are species-specific and can change during embryogenesis or post-embryonic life. During <em>Drosophila</em> embryogenesis, the NC condenses along the Anterior-Posterior (AP) axis in a stereotypical manner, bringing neuromeres closer together. This process has revealed several key parameters, including its morphogenetic mechanics, the roles of various cellular, molecular, and structural components, and the functional purpose of its balanced design. The embryonic NC serves as a valuable model for investigating the ancient mechanisms underlying the structural organization, sensory integration, and motor coordination of the CNS. While many aspects of ganglionic fusion remain unknown, ongoing research promises to provide a more comprehensive understanding of the mechanical and evolutionary principles that govern it.</div></div>","PeriodicalId":36123,"journal":{"name":"Cells and Development","volume":"180 ","pages":"Article 203973"},"PeriodicalIF":3.9,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}