Developmental Dynamics最新文献

{"title":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.734","DOIUrl":"https://doi.org/10.1002/dvdy.734","url":null,"abstract":"<p>Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in <i>Developmental Dynamics</i> that illustrate the complex dynamics of developmental biology.</p><p><b>Limb Development</b> “The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration” by Alejandro Castilla-Ibeas, Sofía Zdral, Kerby Oberg, and Marian Ros. <i>Dev Dyn</i>. 253:9, pp. 798–814. https://doi.org/10.1002/dvdy.695. Limbs, which are crucial for locomotion, are thought to have evolved from fins in an aquatic ancestor as an adaptation to shallow water. Over time, limbs acquired complex characteristics built upon anterior-posterior, proximal-distal, and dorsal-ventral axes. Although limb development and patterning has been well studied, we still have much to learn about the dorsal-ventral axis. The dorsal domain of the limb houses the extensor muscles, ligaments, tendons, nerves, and vessels, whereas the ventral region contains flexor muscles among other tissues and structures. This review discusses our current understanding of dorsal-ventral patterning of the limb, bringing together the results of classic experiments with modern research, concepts, and interpretations. With an emphasis on Lmx1b, which specifies dorsal character and subsequently fate, the authors consider the role of dorsal-ventral patterning in the evolution of paired appendages and the association of variants in LMX1B in association with nail-patella syndrome. Finally, the role of dorsoventral patterning and polarity in digit tip regeneration in mammals is also considered further informing our understanding of limb function and evolutionary adaptations.</p><p><b>Neurodevelopment</b> “Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia” by Carlo Donato Caiaffa, Yogeshwari Ambekar, Manmohan Singh, Ying Linda Lin, Bogdan Wlodarczyk, Salavat Aglyamov, Giuliano Scarcelli, Kirill Larin, and Richard Finnell. <i>Dev Dyn</i>. 253:9, pp. 846–858. https://doi.org/10.1002/dvdy.702. Neurulation is the process of neural tube formation from the neural plate, which subsequently forms the central nervous system, while also contributing to the peripheral nervous system. Perturbation of the early steps of neurulation can lead to neural tube defects, which are one of the most common birth defects, affecting about two in every 100 live births, or about 300,000 cases per year worldwide. Genetic mutations, environmental factors, and nutritional imbalances critically underpin the pathogenesis of most neural tube defects. The Fuz gene forms part of a macromolecular planar polarity effector required for ciliogenesis, and consequently, <i>Fuz</i> knockout mice exhibi","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 9","pages":"796-797"},"PeriodicalIF":2.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.734","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142137664","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}

{"title":"Developmental ecology in embryos of an estuarine pupfish endemic of the Yucatan peninsula: Survival out of water, metabolic depression, and asynchronous hatching","authors":"Omar Domínguez-Castanedo,&nbsp;Sharon Valdez-Carbajal","doi":"10.1002/dvdy.732","DOIUrl":"10.1002/dvdy.732","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Theory predicts that drought-resistant embryos with extended incubations are evolutionarily favored in environments with high mortality of larvae but safe for eggs. Here, we experimentally test, under common garden conditions, the effect of three incubation temperatures and media on embryonic developmental length, extended incubation out of the water, survival, metabolic rate, and hatching dynamics in the estuarine pupfish <i>Garmanella pulchra</i>. We also described the morphological changes of embryonic cortical structures related to air exposure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that embryos incubated out of water in low and medium temperatures present an extended incubation period beyond their hatching capability with a deep metabolic depression. Also, these embryos exhibited a hatching asynchrony not related to water availability. Embryos incubated at high temperatures did not show extended incubation, with decreased probability of survival out of water. Our morphological observations of the embryonic cortical structures reveal that the perivitelline space and hair-like filaments buffer the deleterious drought effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results reveal that <i>G. pulchra</i> possesses life-history traits typical of two separate phenomena: delay hatching and diapause; supporting a true continuum between them, rather than a dichotomy. The evolution of these traits may respond to aerial exposure during low tides in the estuaries of Yucatán they inhabit.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 1","pages":"61-73"},"PeriodicalIF":2.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016694","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}

{"title":"Increased Netrin downstream of overactive Hedgehog signaling disrupts optic fissure formation","authors":"Sarah Lusk,&nbsp;Sarah LaPotin,&nbsp;Jason S. Presnell,&nbsp;Kristen M. Kwan","doi":"10.1002/dvdy.733","DOIUrl":"10.1002/dvdy.733","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Uveal coloboma, a developmental eye defect, is caused by failed development of the optic fissure, a ventral structure in the optic stalk and cup where axons exit the eye and vasculature enters. The Hedgehog (Hh) signaling pathway regulates optic fissure development: loss-of-function mutations in the Hh receptor <i>ptch2</i> produce overactive Hh signaling and can result in coloboma. We previously proposed a model where overactive Hh signaling disrupts optic fissure formation by upregulating transcriptional targets acting both cell- and non-cell-autonomously. Here, we examine the Netrin family of secreted ligands as candidate Hh target genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We find multiple Netrin ligands upregulated in the zebrafish <i>ptch2</i> mutant during optic fissure development. Using a gain-of-function approach to overexpress Netrin in a spatiotemporally specific manner, we find that <i>netrin1a</i> or <i>netrin1b</i> overexpression is sufficient to cause coloboma and disrupt wild-type optic fissure formation. We used loss-of-function alleles, CRISPR/Cas9 mutagenesis, and morpholino knockdown to test if loss of Netrin can rescue coloboma in the <i>ptch2</i> mutant: loss of <i>netrin</i> genes does not rescue the <i>ptch2</i> mutant phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest that Netrin is sufficient but not required to disrupt optic fissure formation downstream of overactive Hh signaling in the <i>ptch2</i> mutant.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 2","pages":"158-173"},"PeriodicalIF":2.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016695","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}

{"title":"Hydrocortisone treatment as a tool to study conjunctival placode induction","authors":"Paige M. Drake,&nbsp;Tamara A. Franz-Odendaal","doi":"10.1002/dvdy.729","DOIUrl":"10.1002/dvdy.729","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Conjunctival placodes are a series of placodes that develop into the conjunctival (scleral) papillae and ultimately induce a series of scleral ossicles in the eyes of many vertebrates. This study establishes a hydrocortisone injection procedure (incl. dosage) that consistently inhibits all conjunctival papillae in the embryonic chicken eye. The effects of this hydrocortisone treatment on apoptosis, vasculature, and placode-related gene expression were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hydrocortisone treatment does not increase apoptotic cell death or have a major effect on the ciliary artery or vascular plexus in the eye. <i>β-catenin</i> and <i>Eda</i> expression levels were not significantly altered following hydrocortisone treatment, despite the absence of conjunctival papillae. Notably, <i>Fgf20</i> expression was significantly reduced following hydrocortisone treatment, and the distribution of <i>β-catenin</i> was altered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study showed that conjunctival papillae induction begins as early as HH27.5 (E5.5). Hydrocortisone treatment reduces <i>Fgf20</i> expression independently of <i>β-catenin</i> and <i>Eda</i> and may instead affect other members of the <i>Wnt</i>/<i>β-catenin</i> or <i>Eda/Edar</i> pathways, or it may affect the ability of morphogens to diffuse through the extracellular matrix. This study contributes to a growing profile of gene expression data during placode development and enhances our understanding of how some vertebrate eyes develop these fascinating bones.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 1","pages":"74-93"},"PeriodicalIF":2.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888760","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}

{"title":"Modulation of mechanosensitive genes during embryonic aortic arch development","authors":"Hummaira Banu Siddiqui,&nbsp;Tansu Golcez,&nbsp;Merve Çelik,&nbsp;Börteçine Sevgin,&nbsp;Mervenur Çoban,&nbsp;İlke Süder,&nbsp;Özen Kaya,&nbsp;Nesrin Özören,&nbsp;Kerem Pekkan","doi":"10.1002/dvdy.728","DOIUrl":"10.1002/dvdy.728","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early embryonic aortic arches (AA) are a dynamic vascular structures that are in the process of shaping into the great arteries of cardiovascular system. Previously, a time-lapsed mechanosensitive gene expression map was established for AA subject to altered mechanical loads in the avian embryo. To validate this map, we investigated effects on vascular microstructure and material properties following the perturbation of key genes using an in-house microvascular gene knockdown system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All siRNA vectors show a decrease in the expression intensity of desired genes with no significant differences between vectors. In TGFβ3 knockdowns, we found a reduction in expression intensities of TGFβ3 (≤76%) and its downstream targets such as ELN (≤99.6%), Fbn1 (≤60%), COL1 (≤52%) and COL3 (≤86%) and an increase of diameter in the left AA (23%). MMP2 knockdown also reduced expression levels in MMP2 (≤30%) and a 6-fold increase in its downstream target COL3 with a decrease in stiffness of the AA wall and an increase in the diameter of the AA (55%). These in vivo measurements were confirmed using immunohistochemistry, western blotting and a computational growth model of the vascular extracellular matrix (ECM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Localized spatial genetic modification of the aortic arch region governs the vascular phenotype and ECM composition of the embryo and can be integrated with mechanically-induced congenital heart disease models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 3","pages":"222-239"},"PeriodicalIF":2.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.728","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888761","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}

{"title":"Editorial highlights","authors":"Paul A. Trainor","doi":"10.1002/dvdy.730","DOIUrl":"10.1002/dvdy.730","url":null,"abstract":"&lt;p&gt;Every organism is a model organism for understanding development, evolution, disease, and regeneration, and we have only begun to scratch the surface of the interdisciplinary genetic, molecular, cellular, and developmental mechanisms that regulate these biological processes. These “Highlights” denote exciting advances recently reported in &lt;i&gt;Developmental Dynamics&lt;/i&gt; that illustrate the complex dynamics of developmental biology.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Organogenesis—Lung Biology&lt;/b&gt; “Evolving topological order in the postnatal visceral pleura” by Betty Liu, Ali Ali, Stacey Kwan, Jennifer Pan, Willi Wagner, Hassan Khalil, Zi Chen, Maximilian Ackermann, and Steven Mentzer; &lt;i&gt;Dev Dyn&lt;/i&gt; 253:8, pp. 711–721. https://doi.org/10.1002/dvdy.688. The surface of a visceral organ is lined by layers of epithelial cells that provide a selective barrier to the surrounding environment. Within these layers, epithelial cells exhibit complex shapes characterized by the number of sides adjoining neighboring cells, and polygonal shapes are associated with optimal cell packing and minimal free surface energy. Proper development of the lung requires rapid growth during the postnatal period with physical interactions between the visceral pleura and subjacent alveoli, which are exposed to both static and dynamic forces that influence cell shape and orientation. In this study, the authors investigated postnatal lung development discovering a high degree of network heterogeneity in which a small number of highly connected nodes, or hubs, play crucial roles in maintaining the network's structural integrity. Furthermore, this facilitated efficient information flow during the challenges of rapid lung growth. Taken together, changes in epithelial cell shape reflect optimal cell packing and the minimization of surface free energy, but also cell–cell interactions, cell proliferation, and cytoskeletal rearrangements, each of which is critical for normal lung development.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Organogenesis—Cochlea Development&lt;/b&gt; “Localization of cadherins in the postnatal cochlear epithelium and their relation to space formation” by Holly Beaulac and Vidhya Munnamalai; &lt;i&gt;Dev Dyn&lt;/i&gt; 253:8, pp. 771–780. https://doi.org/10.1002/dvdy.692. The cochlea is a fluid-filled spiral cavity within the inner ear, that contains the organ of Corti. Comprised of three rows of outer hair cells and one row of inner hair cells in humans, the organ of Corti produces nerve impulses in response to sound vibrations. The organ of Corti has therefore been called the “temple of hearing” in the inner ear. The sensory epithelium in the organ of Corti consists of mechanosensory hair cells intercalated by epithelial support cells. The support cells are stiff yet compliant enough to withstand and modulate vibrations to the hair cells, and the cell adhesion properties of adjoining cell membranes between cells are flexible to allow the formation of fluid-filled spaces within the cochlea. This study investigated the role of cadherin","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 8","pages":"710"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859331","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}

{"title":"Transcription factor Meis1b regulates craniofacial morphogenesis in zebrafish","authors":"Viktorie Psutkova,&nbsp;Petr Nickl,&nbsp;Veronika Brezinova,&nbsp;Olga Machonova,&nbsp;Ondrej Machon","doi":"10.1002/dvdy.731","DOIUrl":"10.1002/dvdy.731","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Meis family of transcription factors operates in Pbx-Meis-Hox regulatory network controlling development of various tissues including eye, limbs, heart, hindbrain or craniofacial skeletal elements originating from the neural crest. Although studies in mouse provide abundant information about Meis factors function in embryogenesis, little is known about their role in zebrafish.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We generated zebrafish lines carrying null mutations in <i>meis1a</i>, <i>meis1b</i>, <i>meis2a</i>, and <i>meis2b</i> genes. Only <i>meis1b</i> mutants are lethal at larval stage around 13 dpf whereas the other mutant lines are viable and fertile. We focused on development of neural crest-derived craniofacial structures such as tendons, cranial nerves, cartilage and accompanying muscles. <i>Meis1b</i> mutants displayed morphogenetic abnormalities in the cartilage originating from the first and second pharyngeal arches. Meckel's cartilage was shorter and wider with fused anterior symphysis and abnormal chondrocyte organization. This resulted in impaired tendons and muscle fiber connections while tenocyte development was not largely affected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Loss-of-function mutation in <i>meis1b</i> affects cartilage morphology in the lower jaw that leads to disrupted organization of muscles and tendons.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"254 1","pages":"40-60"},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859330","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}

{"title":"Disruption of the creb3l1 gene causes defects in caudal fin regeneration and patterning in zebrafish Danio rerio","authors":"Peyton E. VanWinkle,&nbsp;Eunjoo Lee,&nbsp;Bridge Wynn,&nbsp;Tomasz J. Nawara,&nbsp;Holly Thomas,&nbsp;John Parant,&nbsp;Cecilia Alvarez,&nbsp;Rosa Serra,&nbsp;Elizabeth Sztul","doi":"10.1002/dvdy.726","DOIUrl":"10.1002/dvdy.726","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The gene cAMP-Responsive Element Binding protein 3-like-1 (<i>CREB3L1</i>) has been implicated in bone development in mice, with <i>CREB3L1</i> knock-out mice exhibiting fragile bones, and in humans, with <i>CREB3L1</i> mutations linked to osteogenesis imperfecta. However, the mechanism through which Creb3l1 regulates bone development is not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>To probe the role of Creb3l1 in organismal physiology, we used CRISPR-Cas9 genome editing to generate a <i>Danio rerio</i> (zebrafish) model of Creb3l1 deficiency. In contrast to mammalian phenotypes, the Creb3l1 deficient fish do not display abnormalities in osteogenesis, except for a decrease in the bifurcation pattern of caudal fin. Both, skeletal morphology and overall bone density appear normal in the mutant fish. However, the regeneration of caudal fin postamputation is significantly affected, with decreased overall regenerate and mineralized bone area. Moreover, the mutant fish exhibit a severe patterning defect during regeneration, with a significant decrease in bifurcation complexity of the fin rays and distalization of the bifurcation sites. Analysis of genes implicated in bone development showed aberrant patterning of <i>shha</i> and <i>ptch2</i> in Creb3l1 deficient fish, linking Creb3l1 with Sonic Hedgehog signaling during fin regeneration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results uncover a novel role for Creb3l1 in regulating tissue growth and patterning during regeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 12","pages":"1106-1129"},"PeriodicalIF":2.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603429","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}

{"title":"BMP4 regulates asymmetric Pkd2 distribution in mouse nodal immotile cilia and ciliary mechanosensing required for left-right determination.","authors":"Takanobu A Katoh, Tim Lange, Yoshiro Nakajima, Kenta Yashiro, Yasushi Okada, Hiroshi Hamada","doi":"10.1002/dvdy.727","DOIUrl":"https://doi.org/10.1002/dvdy.727","url":null,"abstract":"<p><strong>Background: </strong>Mouse nodal immotile cilia mechanically sense the bending direction for left-right (L-R) determination and activate the left-side-specific signaling cascade, leading to increased Nodal activity. Asymmetric distribution of Pkd2, a crucial channel for L-R determination, on immotile cilia has been reported recently. However, the causal relationship between the asymmetric Pkd2 distribution and direction-dependent flow sensing is not well understood. Furthermore, the underlying molecular mechanism directing this asymmetric Pkd2 distribution remains unclear.</p><p><strong>Results: </strong>The effects of several recombinant proteins and inhibitors on the Pkd2 distribution were analyzed using super-resolution microscopy. Notably, bone morphogenetic protein 4 (BMP4) affected the Pkd2 distribution. Additionally, three-dimensional manipulation of nodal immotile cilia using optical tweezers revealed that excess BMP4 caused defects in the mechanosensing ability of the cilia.</p><p><strong>Conclusions: </strong>Experimental data together with model calculations suggest that BMP4 regulates the asymmetric distribution of Pkd2 in nodal immotile cilia, thereby affecting the ability of these cilia to sense the bending direction for L-R determination. This study, for the first time, provides insight into the relationship between the asymmetric protein distribution in cilia and their function.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562848","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}

{"title":"Actin cytoskeletal regulation of ciliogenesis in development and disease","authors":"Brittany M. Hufft-Martinez,&nbsp;Henry H. Wang,&nbsp;Irfan Saadi,&nbsp;Pamela V. Tran","doi":"10.1002/dvdy.724","DOIUrl":"10.1002/dvdy.724","url":null,"abstract":"<p>Primary cilia are antenna-like sensory organelles that are evolutionarily conserved in nearly all modern eukaryotes, from the single-celled green alga, <i>Chlamydomonas reinhardtii</i>, to vertebrates and mammals. Cilia are microtubule-based cellular projections that have adapted to perform a broad range of species-specific functions, from cell motility to detection of light and the transduction of extracellular mechanical and chemical signals. These functions render cilia essential for organismal development and survival. The high conservation of cilia has allowed for discoveries in <i>C. reinhardtii</i> to inform our understanding of the basic biology of mammalian primary cilia, and to provide insight into the genetic etiology of ciliopathies. Over the last two decades, a growing number of studies has revealed that multiple aspects of ciliary homeostasis are regulated by the actin cytoskeleton, including centrosome migration and positioning, vesicle transport to the basal body, ectocytosis, and ciliary-mediated signaling. Here, we review actin regulation of ciliary homeostasis, and highlight conserved and divergent mechanisms in <i>C. reinhardtii</i> and mammalian cells. Further, we compare the disease manifestations of patients with ciliopathies to those with mutations in actin and actin-associated genes, and propose that primary cilia defects caused by genetic alteration of the actin cytoskeleton may underlie certain birth defects.</p>","PeriodicalId":11247,"journal":{"name":"Developmental Dynamics","volume":"253 12","pages":"1076-1093"},"PeriodicalIF":2.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvdy.724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491267","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}