Developmental Dynamics[JOURNAL]
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200 papers
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Trainor PA
Dev Dyn · 2024 Jul · PMID 38949296 · Publisher ↗
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Rapid generation of single-insertion transgenics by Tol2 transposition in zebrafish.
Kalvaitytė M, Gabrilavičiūtė S, Balciunas D
Dev Dyn · 2024 Nov · PMID 38946125 · Publisher ↗
BACKGROUND: The Tol2 transposable element is the most widely used transgenesis tool in zebrafish. However, its high activity almost always leads to multiple unlinked integrations of the transgenic cassette in F fish. Eac...
BACKGROUND: The Tol2 transposable element is the most widely used transgenesis tool in zebrafish. However, its high activity almost always leads to multiple unlinked integrations of the transgenic cassette in F fish. Each of these transgenes is susceptible to positional effects from the surrounding regulatory landscape, which can lead to altered expression and, consequently, activity. Scientists therefore must strike a balance between the need to maximize reproducibility by establishing single-insertion transgenic lines and the need to complete experiments within a reasonable timeframe. RESULTS: In this article, we introduce a simple competitive dilution strategy for rapid generation of single-insertion transgenics. By using cry:BFP reporter plasmid as a competitor, we achieved a nearly fourfold reduction in the number of the transgene of interest integrations while simultaneously increasing the proportion of single-insertion F generation transgenics to over 50%. We also observed variations in transgene of interest expression among independent single-insertion transgenics, highlighting that the commonly used ubiquitous ubb promoter is susceptible to position effects. CONCLUSIONS: Wide application of our competitive dilution strategy will save time, reduce animal usage, and improve reproducibility of zebrafish research.
Differential retinoic acid sensitivity of oral and pharyngeal teeth in medaka (Oryzias latipes) supports the importance of pouch-cleft contacts in pharyngeal tooth initiation.
Larionova D, Huysseune A
Dev Dyn · 2024 Dec · PMID 38940489 · Publisher ↗
BACKGROUND: Previous studies have claimed that pharyngeal teeth in medaka (Oryzias latipes) are induced independent of retinoic acid (RA) signaling, unlike in zebrafish (Danio rerio). In zebrafish, pharyngeal tooth forma...
BACKGROUND: Previous studies have claimed that pharyngeal teeth in medaka (Oryzias latipes) are induced independent of retinoic acid (RA) signaling, unlike in zebrafish (Danio rerio). In zebrafish, pharyngeal tooth formation depends on a proper physical contact between the embryonic endodermal pouch anterior to the site of tooth formation, and the adjacent ectodermal cleft, an RA-dependent process. Here, we test the hypothesis that a proper pouch-cleft contact is required for pharyngeal tooth formation in embryonic medaka, as it is in zebrafish. We used 4-[diethylamino]benzaldehyde (DEAB) to pharmacologically inhibit RA production, and thus pouch-cleft contacts, in experiments strictly controlled in time, and analyzed these using high-resolution imaging. RESULTS: Pharyngeal teeth in medaka were present only when the corresponding anterior pouch had reached the ectoderm (i.e., a physical pouch-cleft contact established), similar to the situation in zebrafish. Oral teeth were present even when the treatment started approximately 4 days before normal oral tooth appearance. CONCLUSIONS: RA dependency for pharyngeal tooth formation is not different between zebrafish and medaka. We propose that the differential response to DEAB of oral versus pharyngeal teeth in medaka could be ascribed to the distinct germ layer origin of the epithelia involved in tooth formation in these two regions.
Molecular anatomy of emerging Xenopus left-right organizer at successive developmental stages.
Petri N, Vetrova A, Tsikolia N … +1 more , Kremnyov S
Dev Dyn · 2025 Aug · PMID 38934270 · Full text
BACKGROUND: Vertebrate left-right symmetry breaking is preceded by formation of left-right organizer. In Amphibian, this structure is formed by gastrocoel roof plate, which emerges from superficial suprablastoporal cells...
BACKGROUND: Vertebrate left-right symmetry breaking is preceded by formation of left-right organizer. In Amphibian, this structure is formed by gastrocoel roof plate, which emerges from superficial suprablastoporal cells. GRP is subdivided into medial area, which generates leftward flow by rotating monocilia and lateral Nodal1 expressing areas, which are involved in sensing of the flow. After successful symmetry breaking, medial cells are incorporated into a deep layer where they contribute to the axial mesoderm, while lateral domains join somitic mesoderm. RESULTS: Here, we performed detailed analysis of spatial and temporal gene expression of important markers and the corresponding morphology of emerging GRP. Endodermal marker Sox17 and markers of superficial mesoderm display complementary patterns at all studied stages. At early stages, GRP forms Tekt2 positive epithelial domain clearly separated from underlying deep layers, while at later stages, this separation disappears. Marker of early somitic mesoderm MyoD1 was absent in emerging GRP and was induced together with Nodal1 during early neurulation. Decreasing morphological separation is accompanied by lateral to medial covering of GRP by endoderm. CONCLUSION: Our data supports continuous link between superficial mesoderm at the start of gastrulation and mature GRP and suggests late induction of somitic fate in lateral GRP.
Morphologically defined substages of tail morphogenesis in C. elegans males.
Kiontke K, Fernandez P, Woronik A … +1 more , Fitch DHA
Dev Dyn · 2024 Dec · PMID 38924277 · Full text
BACKGROUND: Sex-specific morphogenesis occurs in Caenorhabditis elegans in the vulva of the hermaphrodite and in the male tail during the last larval stage. Temporal progression of vulva morphogenesis has been described...
BACKGROUND: Sex-specific morphogenesis occurs in Caenorhabditis elegans in the vulva of the hermaphrodite and in the male tail during the last larval stage. Temporal progression of vulva morphogenesis has been described in fine detail. However, a similar precise description of male tail morphogenesis was lacking. RESULTS: We here describe morphogenesis of the male tail at time points matching vulva development with special focus on morphogenesis of the tail tip. Using fluorescent reporters, we follow changes in cell shapes, cell fusions, nuclear migration, modifications in the basement membrane, and formation of a new apical extracellular matrix at the end of the tail. CONCLUSION: Our analysis answers two open questions about tail tip morphogenesis (TTM) by showing that one of the four tail tip cells, hyp11, remains largely separate, while the other cells fully fuse with each other and with two additional tail cells to form a ventral tail syncytium. This merger of cells begins at the apical surface early during TTM but is only completed toward the end of the process. This work provides a framework for future investigations of cell biological factors that drive male tail morphogenesis.
The dishevelled associated activator of morphogenesis protein 2 (Daam2) regulates neural tube closure.
Nama K, Su B, Marquez J … +2 more , Khokha MK, Habas R
Dev Dyn · 2024 Dec · PMID 38877839 · Full text
BACKGROUND: The Wnt signaling pathway is highly conserved in metazoans and regulates a large array of cellular processes including motility, polarity and fate determination, and stem cell homeostasis. Modulation of the a...
BACKGROUND: The Wnt signaling pathway is highly conserved in metazoans and regulates a large array of cellular processes including motility, polarity and fate determination, and stem cell homeostasis. Modulation of the actin cytoskeleton via the non-canonical Wnt pathway regulate cell polarity and cell migration that are required for proper vertebrate gastrulation and subsequent neurulation. However, the mechanism(s) of how the non-canonical pathway mediates actin cytoskeleton modulation is not fully understood. RESULTS: Herein, we characterize the role of the Formin-homology protein; dishevelled associated activator of morphogenesis 2 (Daam2) protein in the Wnt signaling pathway. Co-immunoprecipitation assays confirm the binding of Daam2 to dishevelled2 (Dvl2) as well as the domains within these proteins required for interaction; additionally, the interaction between Daam2 and Dvl2 was Wnt-regulated. Sub-cellular localization studies reveal Daam2 is cytoplasmic and regulates the cellular actin cytoskeleton by modulating actin filament formation. During Xenopus development, a knockdown or loss of Daam2 specifically produces neural tube closure defects indicative of a role in non-canonical signaling. Additionally, our studies did not identify any role for Daam2 in canonical Wnt signaling in mammalian culture cells or the Xenopus embryo. CONCLUSIONS: Our studies together identify Daam2 as a component of the non-canonical Wnt pathway and Daam2 is a regulator of neural tube morphogenesis during vertebrate development.
Transcriptional regulators with broad expression in the zebrafish spinal cord.
England SJ, Campbell PC, Banerjee S … +4 more , Bates RL, Grieb G, Fancher WF, Lewis KE
Dev Dyn · 2024 Nov · PMID 38850245 · Publisher ↗
BACKGROUND: The spinal cord is a crucial part of the vertebrate CNS, controlling movements and receiving and processing sensory information from the trunk and limbs. However, there is much we do not know about how this e...
BACKGROUND: The spinal cord is a crucial part of the vertebrate CNS, controlling movements and receiving and processing sensory information from the trunk and limbs. However, there is much we do not know about how this essential organ develops. Here, we describe expression of 21 transcription factors and one transcriptional regulator in zebrafish spinal cord. RESULTS: We analyzed the expression of aurkb, foxb1a, foxb1b, her8a, homeza, ivns1abpb, mybl2b, myt1a, nr2f1b, onecut1, sall1a, sall3a, sall3b, sall4, sox2, sox19b, sp8b, tsc22d1, wdhd1, zfhx3b, znf804a, and znf1032 in wild-type and MIB E3 ubiquitin protein ligase 1 zebrafish embryos. While all of these genes are broadly expressed in spinal cord, they have distinct expression patterns from one another. Some are predominantly expressed in progenitor domains, and others in subsets of post-mitotic cells. Given the conservation of spinal cord development, and the transcription factors and transcriptional regulators that orchestrate it, we expect that these genes will have similar spinal cord expression patterns in other vertebrates, including mammals and humans. CONCLUSIONS: Our data identify 22 different transcriptional regulators that are strong candidates for playing different roles in spinal cord development. For several of these genes, this is the first published description of their spinal cord expression.
Proteomic profiling of TBC1 domain family member 21-null sperms reveals the critical roles of TEKT 1 in their tail defects.
Pan PY, Ke CC, Wang YY … +6 more , Lin YH, Ku WC, Au CF, Chan CC, Huang CY, Lin YH
Dev Dyn · 2024 Nov · PMID 38822685 · Publisher ↗
BACKGROUND: Approximately 7% of the males exhibit reduced fertility; however, the regulatory genes and pathways involved remain largely unknown. TBC1 domain family member 21 (TBC1D21) contains a conserved RabGAP catalyti...
BACKGROUND: Approximately 7% of the males exhibit reduced fertility; however, the regulatory genes and pathways involved remain largely unknown. TBC1 domain family member 21 (TBC1D21) contains a conserved RabGAP catalytic domain that induces GDP/GTP exchange to inactivate Rabs by interacting with microtubules. We previously reported that Tbc1d21-null mice exhibit severe sperm tail defects with a disrupted axoneme, and that TBC1D21 interacts with RAB10. However, the pathological mechanisms underlying the Tbc1d21 loss-induced sperm tail defects remain unknown. RESULTS: Murine sperm from wild-type and Tbc1d21-null mice were comparatively analyzed using proteomic assays. Over 1600 proteins were identified, of which 15 were significantly up-regulated in Tbc1d21-null sperm. Notably, several tektin (TEKT) family proteins, belonging to a type of intermediate filament critical for stabilizing the microtubular structure of cilia and flagella, were significantly up-regulated in Tbc1d21 sperm. We also found that TBC1D21 interacts with TEKT1. In addition, TEKT1 co-localized with RAB10 during sperm tail formation. Finally, we found Tbc1d21-null sperm exhibited abnormal accumulation of TEKT1 in the midpiece region, accompanied by disrupted axonemal structures. CONCLUSIONS: These results reveal that TBC1D21 modulates TEKTs protein localization in the axonemal transport system during sperm tail formation.
Development of node architecture and emergence of molecular organizer characteristics in the pig embryo.
Harmoush B, Viebahn C, Tsikolia N
Dev Dyn · 2025 Aug · PMID 38733144 · Full text
BACKGROUND: The avian node is the equivalent of the amphibian Spemann's organizer, as indicated by its ability to induce a secondary axis, cellular contribution, and gene expression, whereas the node of the mouse, which...
BACKGROUND: The avian node is the equivalent of the amphibian Spemann's organizer, as indicated by its ability to induce a secondary axis, cellular contribution, and gene expression, whereas the node of the mouse, which displays limited inductive capacities, was suggested to be a part of spatially distributed signaling. Furthermore, the structural identity of the mouse node is subject of controversy, while little is known about equivalent structures in other mammals. RESULTS: We analyzed the node and emerging organizer in the pig using morphology and the expression of selected organizer genes prior to and during gastrulation. The node was defined according to the "four-quarter model" based on comparative consideration. The node of the pig displays a multilayered, dense structure that includes columnar epithelium, bottle-like cells in the dorsal part, and mesenchymal cells ventrally. Expression of goosecoid (gsc), chordin, and brachyury, together with morphology, reveal the consecutive emergence of three distinct domains: the gastrulation precursor domain, the presumptive node, and the mature node. Additionally, gsc displays a ventral expression domain prior to epiblast epithelialization. CONCLUSION: Our study defines the morphological and molecular context of the emerging organizer equivalent in the pig and suggests a sequential development of its function.
Stress granule related-genes during blastogenetic cycle of two colonial ascidians: Botryllus schlosseri compared to Botryllus primigenus.
Drago L, Sasada T, Sunanaga T … +1 more , Ballarin L
Dev Dyn · 2025 Jan · PMID 38727221 · Publisher ↗
BACKGROUND: Colonial ascidians are chordates known to reproduce both sexually and asexually. In the present study, we used the Mediterranean species Botryllus schlosseri and the Japanese Botryllus primigenus to investiga...
BACKGROUND: Colonial ascidians are chordates known to reproduce both sexually and asexually. In the present study, we used the Mediterranean species Botryllus schlosseri and the Japanese Botryllus primigenus to investigate the possible role of tiar, ttp, and g3bp in the periodical renewal of the colonies, defined by generation changes or takeovers. In this scenario, the above genes, which codify key components for the formation of stress granules, storing specific mRNAs, can play a pivotal role, allowing the regulation of processes such as stress responses, cell proliferation, and stem cell development. RESULTS: We characterized tiarx1, ttp, and g3bp2 sequences in B. schlosseri and B. primigenus. Then, we analyzed gene transcription by in situ hybridization in hemolymph cells and colony tissues, and we proceeded with quantification of the gene transcription by quantitative real‐time PCR, during the phases of the colonial blastogenetic cycle. CONCLUSIONS: Our results allowed us to assign a role in the development of the new colonial generations to the studied genes.
Embryology of the fat-tailed dunnart (Sminthopsis crassicaudata): A marsupial model for comparative mammalian developmental and evolutionary biology.
Newton AH, Hutchison JC, Farley ER … +13 more , Scicluna EL, Youngson NA, Liu J, Menzies BR, Hildebrandt TB, Lawrence BM, Sutherland AHW, Potter DL, Tarulli GA, Selwood L, Frankenberg S, Ord S, Pask AJ
Dev Dyn · 2025 Feb · PMID 38721717 · Full text
BACKGROUND: Marsupials are a diverse and unique group of mammals, but remain underutilized in developmental biology studies, hindering our understanding of mammalian diversity. This study focuses on establishing the fat-...
BACKGROUND: Marsupials are a diverse and unique group of mammals, but remain underutilized in developmental biology studies, hindering our understanding of mammalian diversity. This study focuses on establishing the fat-tailed dunnart (Sminthopsis crassicaudata) as an emerging laboratory model, providing reproductive monitoring methods and a detailed atlas of its embryonic development. RESULTS: We monitored the reproductive cycles of female dunnarts and established methods to confirm pregnancy and generate timed embryos. With this, we characterized dunnart embryo development from cleavage to birth, and provided detailed descriptions of its organogenesis and heterochronic growth patterns. Drawing stage-matched comparisons with other species, we highlight the dunnarts accelerated craniofacial and limb development, characteristic of marsupials. CONCLUSIONS: The fat-tailed dunnart is an exceptional marsupial model for developmental studies, where our detailed practices for reproductive monitoring and embryo collection enhance its accessibility in other laboratories. The accelerated developmental patterns observed in the Dunnart provide a valuable system for investigating molecular mechanisms underlying heterochrony. This study not only contributes to our understanding of marsupial development but also equips the scientific community with new resources for addressing biodiversity challenges and developing effective conservation strategies in marsupials.
Muscular remodeling and anteroposterior patterning during tapeworm segmentation.
Jarero F, Baillie A, Riddiford N … +3 more , Montagne J, Koziol U, Olson PD
Dev Dyn · 2024 Nov · PMID 38689520 · Publisher ↗
BACKGROUND: Tapeworms are parasitic flatworms that independently evolved a segmented body plan, historically confounding comparisons with other animals. Anteroposterior (AP) patterning in free-living flatworms and in tap...
BACKGROUND: Tapeworms are parasitic flatworms that independently evolved a segmented body plan, historically confounding comparisons with other animals. Anteroposterior (AP) patterning in free-living flatworms and in tapeworm larvae is associated with canonical Wnt signaling and positional control genes (PCGs) are expressed by their musculature in regionalized domains along the AP axis. Here, we extend investigations of PCG expression to the adult of the mouse bile-duct tapeworm Hymenolepis microstoma, focusing on the growth zone of the neck region and the initial establishment of segmental patterning. RESULTS: We show that the adult musculature includes new, segmental elements that first appear in the neck and that the spatial patterns of Wnt factors are consistent with expression by muscle cells. Wnt factor expression is highly regionalized and becomes AP-polarized in segments, marking them with axes in agreement with the polarity of the main body axis, while the transition between the neck and strobila is specifically demarcated by the expression domain of a Wnt11 paralog. CONCLUSION: We suggest that segmentation could originate in the muscular system and participate in patterning the AP axis through regional and polarized expression of PCGs, akin to the gene regulatory networks employed by free-living flatworms and other animals.
Enigmatic Nodal and Lefty gene repertoire discrepancy: Latent evolutionary history revealed by vertebrate-wide phylogeny.
Kuraku S
Dev Dyn · 2025 Aug · PMID 38647085 · Full text
Homology in vertebrate body plans is traditionally ascribed to the high-level conservation of regulatory components within the genetic programs governing them, particularly during the "phylotypic stage." However, advance...
Homology in vertebrate body plans is traditionally ascribed to the high-level conservation of regulatory components within the genetic programs governing them, particularly during the "phylotypic stage." However, advancements in embryology and molecular phylogeny have unveiled the dynamic nature of gene repertoires responsible for early development. Notably, the Nodal and Lefty genes, members of the transforming growth factor-beta superfamily producing intercellular signaling molecules and crucial for left-right (L-R) symmetry breaking, exhibit distinctive features within their gene repertoires. These features encompass among-species gene repertoire variations resulting from gene gain and loss, as well as gene conversion. Despite their significance, these features have been largely unexplored in a phylogenetic context, but accumulating genome-wide sequence information is allowing the scrutiny of these features. It has exposed hidden paralogy between Nodal1 and Nodal2 genes resulting from differential gene loss in amniotes. In parallel, the tandem cluster of Lefty1 and Lefty2 genes, which was thought to be confined to mammals, is observed in sharks and rays, with an unexpected phylogenetic pattern. This article provides a comprehensive review of the current understanding of the origins of these vertebrate gene repertoires and proposes a revised nomenclature based on the elucidated history of vertebrate genome evolution.
Reduced mTORC1-signaling in progenitor cells leads to retinal lamination deficits.
Nord C, Jones I, Garcia-Maestre M … +2 more , Hägglund AC, Carlsson L
Dev Dyn · 2024 Oct · PMID 38546215 · Publisher ↗
BACKGROUND: Neuronal lamination is a hallmark of the mammalian central nervous system (CNS) and underlies connectivity and function. Initial formation of this tissue architecture involves the integration of various signa...
BACKGROUND: Neuronal lamination is a hallmark of the mammalian central nervous system (CNS) and underlies connectivity and function. Initial formation of this tissue architecture involves the integration of various signaling pathways that regulate the differentiation and migration of neural progenitor cells. RESULTS: Here, we demonstrate that mTORC1 mediates critical roles during neuronal lamination using the mouse retina as a model system. Down-regulation of mTORC1-signaling in retinal progenitor cells by conditional deletion of Rptor led to decreases in proliferation and increased apoptosis during embryogenesis. These developmental deficits preceded aberrant lamination in adult animals which was best exemplified by the fusion of the outer and inner nuclear layer and the absence of an outer plexiform layer. Moreover, ganglion cell axons originating from each Rptor-ablated retina appeared to segregate to an equal degree at the optic chiasm with both contralateral and ipsilateral projections displaying overlapping termination topographies within several retinorecipient nuclei. In combination, these visual pathway defects led to visually mediated behavioral deficits. CONCLUSIONS: This study establishes a critical role for mTORC1-signaling during retinal lamination and demonstrates that this pathway regulates diverse developmental mechanisms involved in driving the stratified arrangement of neurons during CNS development.
Deciphering adipose development: Function, differentiation and regulation.
Guo G, Wang W, Tu M … +10 more , Zhao B, Han J, Li J, Pan Y, Zhou J, Ma W, Liu Y, Sun T, Han X, An Y
Dev Dyn · 2024 Nov · PMID 38516819 · Publisher ↗
The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming...
The overdevelopment of adipose tissues, accompanied by excess lipid accumulation and energy storage, leads to adipose deposition and obesity. With the increasing incidence of obesity in recent years, obesity is becoming a major risk factor for human health, causing various relevant diseases (including hypertension, diabetes, osteoarthritis and cancers). Therefore, it is of significance to antagonize obesity to reduce the risk of obesity-related diseases. Excess lipid accumulation in adipose tissues is mediated by adipocyte hypertrophy (expansion of pre-existing adipocytes) or hyperplasia (increase of newly-formed adipocytes). It is necessary to prevent excessive accumulation of adipose tissues by controlling adipose development. Adipogenesis is exquisitely regulated by many factors in vivo and in vitro, including hormones, cytokines, gender and dietary components. The present review has concluded a comprehensive understanding of adipose development including its origin, classification, distribution, function, differentiation and molecular mechanisms underlying adipogenesis, which may provide potential therapeutic strategies for harnessing obesity without impairing adipose tissue function.
Disruption of Fuz in mouse embryos generates hypoplastic hindbrain development and reduced cranial nerve ganglia.
Caiaffa CD, Ambekar YS, Singh M … +6 more , Lin YL, Wlodarczyk B, Aglyamov SR, Scarcelli G, Larin KV, Finnell RH
Dev Dyn · 2024 Sep · PMID 38501709 · Full text
BACKGROUND: The brain and spinal cord formation is initiated in the earliest stages of mammalian pregnancy in a highly organized process known as neurulation. Environmental or genetic interferences can impair neurulation...
BACKGROUND: The brain and spinal cord formation is initiated in the earliest stages of mammalian pregnancy in a highly organized process known as neurulation. Environmental or genetic interferences can impair neurulation, resulting in clinically significant birth defects known collectively as neural tube defects. The Fuz gene encodes a subunit of the CPLANE complex, a macromolecular planar polarity effector required for ciliogenesis. Ablation of Fuz in mouse embryos results in exencephaly and spina bifida, including dysmorphic craniofacial structures due to defective cilia formation and impaired Sonic Hedgehog signaling. RESULTS: We demonstrate that knocking Fuz out during embryonic mouse development results in a hypoplastic hindbrain phenotype, displaying abnormal rhombomeres with reduced length and width. This phenotype is associated with persistent reduction of ventral neuroepithelial stiffness in a notochord adjacent area at the level of the rhombomere 5. The formation of cranial and paravertebral ganglia is also impaired in these embryos. CONCLUSIONS: This study reveals that hypoplastic hindbrain development, identified by abnormal rhombomere morphology and persistent loss of ventral neuroepithelial stiffness, precedes exencephaly in Fuz ablated murine mutants, indicating that the gene Fuz has a critical function sustaining normal neural tube development and neuronal differentiation.
Gap junctions in polycystic ovary syndrome: Implications for follicular arrest.
Zhu Y, Zhu H, Wu P
Dev Dyn · 2024 Oct · PMID 38501340 · Publisher ↗
Gap junctions are specialized intercellular conduits that provide a direct pathway between neighboring cells, which are involved in numerous physiological processes, such as cellular differentiation, cell growth, and met...
Gap junctions are specialized intercellular conduits that provide a direct pathway between neighboring cells, which are involved in numerous physiological processes, such as cellular differentiation, cell growth, and metabolic coordination. The effect of gap junctional hemichannels in folliculogenesis is particularly obvious, and the down-regulation of connexins is related to abnormal follicle growth. Polycystic ovary syndrome (PCOS) is a ubiquitous endocrine disorder of the reproductive system, affecting the fertility of adult women due to anovulation. Exciting evidence shows that gap junction is involved in the pathological process related to PCOS and affects the development of follicles in women with PCOS. In this review, we examine the expression of connexins in follicular cells of PCOS and figure out whether such communication could have consequences for PCOS women. While along with results from clinical and related animal studies, we summarize the mechanism of connexins involved in the pathogenesis of PCOS.
Protein signaling and morphological development of the tail fluke in the embryonic beluga whale (Delphinapterus leucas).
Gavazzi LM, Nair M, Suydam R … +3 more , Usip S, Thewissen JGM, Cooper LN
Dev Dyn · 2024 Sep · PMID 38494595 · Full text
BACKGROUND: During the land-to-sea transition of cetaceans (whales, dolphins, and porpoises), the hindlimbs were lost and replaced by an elaborate tail fluke that evolved 32 Ma. All modern cetaceans utilize flukes for li...
BACKGROUND: During the land-to-sea transition of cetaceans (whales, dolphins, and porpoises), the hindlimbs were lost and replaced by an elaborate tail fluke that evolved 32 Ma. All modern cetaceans utilize flukes for lift-based propulsion, and nothing is known of this organ's molecular origins during embryonic development. This study utilizes immunohistochemistry to identify the spatiotemporal location of protein signals known to drive appendage outgrowth in other vertebrates (e.g., Sonic Hedgehog [SHH], GREMLIN [GREM], wingless-type family member 7a [WNT], and fibroblast growth factors [FGFs]) and to test the hypothesis that signals associated with outgrowth and patterning of the tail fluke are similar to a tetrapod limb. Specifically, this study utilizes an embryo of a beluga whale (Delphinapterus leucas) as a case study. RESULTS: Results showed epidermal signals of WNT and FGFs, and mesenchymal/epidermal signals of SHH and GREM. These patterns are most consistent with vertebrate limb development. Overall, these data are most consistent with the hypothesis that outgrowth of tail flukes in cetaceans employs a signaling pattern that suggests genes essential for limb outgrowth and patterning shape this evolutionarily novel appendage. CONCLUSIONS: While these data add insights into the molecular signals potentially driving the evolution and development of tail flukes in cetaceans, further exploration of the molecular drivers of fluke development is required.
Lineage-specific requirements of Alx4 function in craniofacial and hair development.
Lan Y, Wu Z, Liu H … +1 more , Jiang R
Dev Dyn · 2024 Oct · PMID 38481039 · Full text
BACKGROUND: Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes...
BACKGROUND: Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in Alx4 have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of Alx4 expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis. RESULTS: We report generation of Alx4 conditional mice and show that tissue-specific Cre-mediated inactivation of Alx4 in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in Alx4-null mice but without affecting postnatal survival. While Alx4-null mice that survive postnatally exhibited dorsal alopecia, mice lacking Alx4 function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking Alx4 in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development. CONCLUSION: The Alx4 mice provide a valuable resource for systematic investigation of cell type- and stage-specific function of ALX family transcription factors in development and disease.
Analysis of changes in the action potential morphology of the mouse sinoatrial node true pacemaker cells during ontogenetic development in vitro and in silico.
Ryvkin A, Furman A, Lebedeva E … +1 more , Gonotkov M
Dev Dyn · 2024 Oct · PMID 38459937 · Publisher ↗
BACKGROUND: Maturation of the mouse is accompanied by the increase in heart rate. However, the mechanisms underlying this process remain unclear. We performed an action potentials (APs) recordings in mouse sinoatrial nod...
BACKGROUND: Maturation of the mouse is accompanied by the increase in heart rate. However, the mechanisms underlying this process remain unclear. We performed an action potentials (APs) recordings in mouse sinoatrial node (SAN) true pacemaker cells and in silico analysis to clarify the mechanisms underlying pre-postnatal period heart rate changes. RESULTS: The APs of true pacemaker cells at different stages had similar configurations and dV/dt values. The cycle length, action potential duration (APD), maximal diastolic potential (MDP), and AP amplitude decreased, meanwhile the velocity of diastolic depolarization (DDR) increased from E12.5 stage to adult. Using a pharmacological approach we found that in SAN true pacemaker cells ivabradine reduces the DDR and the cycle length significantly stronger in E12.5 than in newborn and adult mice, whereas the effects of Ni and nifedipine were significantly stronger in adult mice. Computer simulations further suggested that the density of the hyperpolarization-activated pacemaker сurrent (I) decreased during development, whereas transmembrane and intracellular Ca flows increased. CONCLUSIONS: The ontogenetic decrease in I density from E12.5 to adult leads to depolarization of MDP to the voltage range in which calcium currents are activated, thereby shifting the balance from the "membrane-clock" to the "calcium-clock."
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