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Lysosome-Related Organelles Orchestrate Guanine Crystal Formation in Pigment Cells

Iridosomes, the guanine crystal-forming organelles of pigment-producing iridophores, are among the most versatile, visually striking yet mechanistically uncharacterized organelles in vertebrate biology. Lysosome-related organelles (LROs) support cell type-specific functions by adapting endolysosomal pathways for specialized roles. Here, we show that iridosomes represent a previously unrecognized subtype of LROs. Using transcriptomic profiling of zebrafish iridophores, CRISPR-Cas9-mediated gene disruption, and cryogenic transmission electron microscopy, we define the molecular program underlying iridosome biogenesis. Iridosomes have evolved unique adaptations for crystal growth while retaining core features of other LROs. Key regulators, including RAB32a, AP3M2, and HPS5, are essential for crystal formation, with gene knockouts causing reduced crystal number, altered morphology, and distinct maturation defects. We further identify hallmark LRO features in iridosomes, including intraluminal vesicles and pH-regulated developmental transitions. Cross-species transcriptomic analysis confirms that iridosomes share an LRO signature across vertebrates, including teleost fish and reptiles, suggesting ancient evolutionary origins. These findings establish iridosomes as crystalline LROs and as a model for investigating how cells construct structurally specialized organelles through coordinated trafficking, acid-base regulation, and crystallization, with implications for LRO evolution and human disease.

developmental biology↗

Novel metrics reveal new structure and unappreciated heterogeneity in C. elegans development

High throughput experimental approaches are increasingly allowing for the quantitative description of cellular and organismal phenotypes. Distilling these large volumes of complex data into meaningful measures that can drive biological insight remains a central challenge. In the quantitative study of development, for instance, one can resolve phenotypic measures for single cells onto their lineage history, enabling joint consideration of heritable signals and cell fate decisions. Most attempts to analyze this type of data, however, discard much of the information content contained within lineage trees. In this work we introduce a generalized metric, which we term the branch distance, that allows us to compare any two embryos based on phenotypic measurements in individual cells. This approach aligns those phenotypic measurements to the underlying lineage tree, providing a flexible and intuitive framework for quantitative comparisons between, for instance, Wild-Type (WT) and mutant developmental programs. We apply this novel metric to data on cell-cycle timing from over 1300 WT and RNAi-treated Caenorhabditis elegans embryos. Our new metric revealed surprising heterogeneity within this data set, including subtle batch effects in WT embryos and dramatic variability in RNAi-induced developmental phenotypes, all of which had been missed in previous analyses. Further investigation of these results suggests a novel, quantitative link between pathways that govern cell fate decisions and pathways that pattern cell cycle timing in the early embryo. Our work demonstrates that the branch distance we propose, and similar metrics like it, have the potential to revolutionize our quantitative understanding of organismal phenotype.

developmental biology↗

Image restoration of degraded time-lapse microscopy data mediated by infrared-imaging.

Time-lapse fluorescence microscopy is key to unraveling the processes underpinning biological development and function. However, living systems, by their nature, permit only a limited toolbox for interrogation. Consequently, following time-lapses, expended samples contain untapped information that is typically discarded. Herein we employ convolutional neural networks (CNNs) to augment the live imaging data using this complementary information. In particular, live, deep tissue imaging is limited by the spectral range of live-cell compatible probes/fluorescent proteins. We demonstrate that CNNs may be used to restore deep-tissue contrast in GFP-based time-lapse imaging using paired final-state datasets acquired using infrared dyes and improve information content accordingly. Surprisingly, the networks are remarkably robust over a wide range of developmental times. We employ said network to GFP time-lapse images captured during zebrafish and drosophila embryo/larval development and demonstrate live, deep tissue image contrast.

developmental biology↗

Integrated transcriptomic analysis reveals a metabolically quiescent state and gene expression networks related to intermediate and mature human 8-cell stage embryo resembling cells in vitro

Human early development is challenging to study due to limited samples and cell numbers. The emergence of 8-cell stage embryo-like cells (8CLCs) offers new opportunities to understand embryonic genome activation (EGA) in humans. Our research compares and characterizes 8CLCs from various stem cell-based systems to determine how well these models reflect human early embryonic development. Using single-cell RNA sequencing (scRNA-seq) datasets from multiple studies, we integrated data to identify key gene co-expression modules, transposable element (TE) expression, and biological processes recapitulated in 8CLCs. We identified both mature and intermediate 8CLCs, with the Yoshihara and Mazid datasets best representing 8-cell stage embryos. 8CLCs show quiescence in energy and RNA metabolism, regulation of RNA splicing, and ribosome biogenesis, mirroring human 8-cell stage embryos. Our findings underscore the importance of distinguishing mature 8CLCs from partially reprogrammed cell states to improve their use as models for human EGA, in vitro.

developmental biology↗

Prenatal cannabinoid exposure induces sex-specific alterations in placental growth and lipid metabolism gene expression

BackgroundPrenatal cannabis use is becoming increasingly more commonplace. However, cannabis exposure is linked to adverse pregnancy outcomes, including gestational hypertension, preeclampsia, and preterm birth. The aim of this study was to determine the morphological and molecular effects of prenatal cannabinoid exposure on the placenta. MethodsPregnant Sprague-Dawley rats were exposed daily to vaporized THC (100 mg/mL) starting at gestational day (GD)5 until GD19 when dams were sacrificed and fetuses and placentas collected. Fetuses were genotyped for genetic sex and transcriptomic analysis was performed on male and female THC-exposed and control placentas. ResultsOn GD19, both the fetuses and placentas from the THC group were significantly larger than the control. When separated by sex, both male and female THC fetuses were significantly larger; however, only male THC placentas were significantly larger than male control placentas with no significant difference in placental weight between female control and THC placentas. RNA-sequencing revealed enriched biological processes related to nutrient transport and lipid catabolism, protein-lipid complex formation, and lipoprotein particle remodeling and organization. Further transcriptomic analysis determined that the differentially expressed genes and enriched biological processes related to lipid metabolism were preferentially enriched in the female THC placentas compared to the male, suggesting a sex-specific effect. DiscussionCollectively, these data present sex-specific effects of prenatal cannabinoid exposure on placental growth and global gene expression. These data also suggest that sex influences gene expression of genes related to lipid metabolism in the THC-exposed placentas.

Developmental Biology↗

Mouse suppressyn-like 1 is an endogenous retrovirus-derived inhibitor of membrane fusion through direct association with envelope glycoproteins

Cell-cell fusion is essential for placental development and is mediated by endogenous retrovirus (ERV)-derived fusogens known as syncytins. However, how ERV-derived proteins negatively regulate membrane fusion remains largely unknown. Here, we identify a previously uncharacterized murine ERV envelope-derived protein, mouse suppressyn-like 1 (mSUPYNL1), that suppresses syncytin-mediated membrane fusion through a mechanism distinct from that of placental human suppressyn (hSUPYN). Unlike hSUPYN, which acts through receptor interference, mSUPYNL1 inhibits both murine and human syncytin-mediated fusion independently of receptor usage by associating with the surface (SU) subunits of multiple syncytin envelope glycoproteins, revealing a receptor-independent mechanism of fusion suppression. This mechanism extends beyond endogenous fusogens. mSUPYNL1 also associates with the SU glycoprotein (gp46) of Human T-cell Leukemia Virus type 1 (HTLV-1) and suppresses Env-dependent syncytium formation, whereas hSUPYN showed no detectable antiviral activity in this assay. These findings identify mSUPYNL1 as a broad-spectrum inhibitor of envelope glycoprotein-mediated membrane fusion. Analysis of mSUPYNL1 knockout mice revealed that, in contrast to the placenta-restricted expression of hSUPYN, mSUPYNL1 was broadly expressed, with its most prominent localization in decidual stromal and vascular endothelial cells of the pregnant uterus, as well as in hematopoietic tissues such as the spleen and thymus. Together, our findings uncover an evolutionarily distinct class of ERV-derived fusion suppressors that function through envelope glycoprotein recognition instead of receptor interference. Our study expands current models of ERV domestication by demonstrating that retroviral envelope proteins have been independently co-opted not only to promote membrane fusion but also to restrain it, thereby linking placental biology, antiviral defense, and host evolution. HIGHLIGHTSO_LImSUPYNL1 is an endogenous retrovirus-derived membrane fusion inhibitor C_LIO_LImSUPYNL1 binds the SU domains of murine and human syncytins C_LIO_LImSUPYNL1 suppresses HTLV-1 Env-mediated syncytium formation C_LIO_LIDirect envelope recognition enables receptor-independent fusion inhibition C_LI

developmental biology↗

Altricial bird early-stage embryos express the molecular "machinery" to respond to maternal thyroid hormone cues

Maternal hormones, such as thyroid hormones transferred to embryos and eggs, are key signalling pathways to mediate maternal effects. To be able to respond to maternal cues, embryos must express key molecular machinery of the hormone pathways, such as enzymes and receptors. While altricial birds begin thyroid hormone (TH) production only at/after hatching, experimental evidence suggests that their phenotype can be influenced by maternal THs deposited in the egg. However, it is not understood, how and when altricial birds express genes in the TH-pathway. For the first time, we measured the expression of key TH-pathway genes in altricial embryos, using two common altricial ecological model species (pied flycatcher, Ficedula hypoleuca and blue tit Cyanistes caeruleus). Deiodinase DIO1 gene expression could not be reliably confirmed in either species, but deiodinase enzyme DIO2 and DIO3 genes were expressed in both species. Given that DIO2 coverts T4 to biologically active T3, and DIO3 mostly T3 to inactive forms of thyroid hormones, our results suggest that embryos may modulate maternal signals. Thyroid hormone receptor (THRA and THRB) and monocarboxyl membrane transporter gene (SLC15A2) were also expressed, enabling TH-responses. Our results suggest that early altricial embryos may be able to respond and potentially modulate maternal signals conveyed by thyroid hormones.

developmental biology↗

Mapping histological and functional maturation of human endocrine pancreas across early postnatal periods

Human endocrine cell differentiation and islet morphogenesis play critical roles in determining islet cell mass and function, but the events and timeline of these processes are incompletely defined. To better understand early human islet cell development and maturation, we collected 115 pediatric pancreata and mapped morphological and spatiotemporal changes from birth through the first ten years of life. Using quantitative analyses and a combination of complementary tissue imaging approaches, including confocal microscopy and whole-slide imaging, we developed an integrated model for endocrine cell formation and islet architecture, including endocrine cell type heterogeneity and abundance, endocrine cell proliferation, and islet vascularization and innervation. We also assessed insulin and glucagon secretory profiles in isolated islet preparations from pediatric donors aged 2 months to 10 years and found a temporal difference in the maturation of insulin secretion compared to glucagon secretion. This comprehensive summary of postnatal and pediatric pancreatic islet development provides a framework for future studies and integration of emerging genetic and genomic data related to islet biology and diabetes risk.

developmental biology↗

How prolonged expression of Hunchback, a temporal transcription factor, re-wires locomotor circuits

AbstractIn many CNS regions, neuronal birth timing is associated with circuit membership. In Drosophila larvae, we show U motor neurons are a temporal cohort--a set of non-identical, contiguously-born neurons from a single neuronal stem cell that contribute to the same circuit. We prolong expression of a temporal transcription factor, Hunchback, to increase the number of U motor neurons with early-born molecular identities. On the circuit level, this expands and re-wires the U motor neuron temporal cohort. On the cell biological level, we find novel roles for Hunchback in motor neuron target selection, neuromuscular synapse formation, dendrite morphogenesis, and behavior. These data provide insight into the relationship between stem cell and circuit, show that Hunchback is a potent regulator of circuit assembly, and suggest that temporal transcription factors are molecules that could be altered during evolution or biomedical intervention for the generation of novel circuits.

developmental biology↗

Aubergine And piRNAs Repress The Proto-Oncogene Cbl For Germline Stem Cell Self-Renewal

PIWI proteins have essential roles in germ cells and stem cell lineages. In Drosophila, Piwi is required in somatic niche cells and germline stem cells (GSCs) for GSC self-renewal and differentiation. Whether and how other PIWI proteins are involved in GSC biology remains unknown. Here, we show that Aubergine (Aub), another PIWI protein, is intrinsically required in GSCs for their self-renewal and differentiation. Aub loading with piRNAs is essential for these functions. The major role of Aub is in self-renewal and depends on mRNA regulation. We identify the Cbl proto-oncogene, a regulator of mammalian hematopoietic stem cells, as a novel GSC differentiation factor. Aub represses Cbl mRNA translation for GSC self-renewal, and does so through recruitment of the CCR4-NOT complex. This study reveals the role of piRNAs and PIWI proteins in translational repression for stem cell homeostasis and highlights piRNAs as major post-transcriptional regulators in key developmental decisions.

developmental biology↗

Machine learning-based estimation of spatial gene expression pattern during ESC-derived retinal organoid development

Organoids, which can reproduce the complex tissue structures found in embryos, are revolutionizing basic research and regenerative medicine. In order to use organoids for research and medicine, it is necessary to assess the composition and arrangement of cell types within the organoid, i.e., spatial gene expression. However, current methods are invasive and require gene editing and immunostaining. In this study, we developed a non-invasive estimation method of spatial gene expression patterns using machine learning. A deep learning model was trained with an encoder-decoder architecture on a dataset of retinal organoids derived from mouse embryonic stem cells. This method successfully estimated spatially plausible fluorescent patterns with appropriate intensities, enabling the non-invasive, quantitative estimation of spatial gene expression patterns within each tissue. Thus, this method could lead to new avenues for evaluating spatial gene expression patterns across a wide range of biology and medicine fields. HighlightsO_LIA non-invasive estimation method of spatial gene expression pattern is proposed C_LIO_LIA CNN architecture is employed to convert a phase-contrast to fluorescence image C_LIO_LIThe method was trained on a dataset of mouse ESC-derived retinal organoids C_LIO_LISpatially plausible patterns of Rx gene expressions were successfully estimated C_LI

developmental biology↗

Heterogeneity and Functional Analysis of Cardiac Fibroblasts in Heart Development

BackgroundAs one of the major cell types in the heart, fibroblasts play critical roles in multiple biological processes. Cardiac fibroblasts are known to develop from multiple sources, but their transcriptional profiles have not been systematically compared. Furthermore, while the function of a few genes in cardiac fibroblasts has been studied, the overall function of fibroblasts as a cell type remains uninvestigated. MethodsSingle-cell mRNA sequencing (scRNA-seq) and bioinformatics approaches were used to analyze the genome-wide genes expression and extracellular matrix genes expression in fibroblasts, as well as the ligand-receptor interactions between fibroblasts and cardiomyocytes. Single molecular in situ hybridization was employed to analyze the expression pattern of fibroblast subpopulation-specific genes. The Diphtheria toxin fragment A (DTA) system was utilized to ablate fibroblasts at each developmental phase. ResultsUsing RNA staining of Col1a1 at different stages, we grouped cardiac fibroblasts into four developmental phases. Through the analysis of scRNA-seq profiles of fibroblasts at 18 stages from two mouse strains, we identified significant heterogeneity, preserving lineage gene expression in their precursor cells. Within the main fibroblast population, we found differential expressions of Wt1, Tbx18, and Aldh1a2 genes in various cell clusters. Lineage tracing studies showed Wt1- and Tbx18-positive fibroblasts originated from respective epicardial cells. Furthermore, using a conditional DTA system-based elimination, we identified the crucial role of fibroblasts in early embryonic and heart growth, but not in neonatal heart growth. Additionally, we identified the zone- and stage-associated expression of extracellular matrix genes and fibroblast-cardiomyocyte ligand-receptor interactions. This comprehensive understanding sheds light on fibroblast function in heart development. ConclusionWe observed cardiac fibroblast heterogeneity at embryonic and neonatal stages, with preserved lineage gene expression. Ablation studies revealed their distinct roles during development, likely influenced by varying extracellular matrix genes and ligand-receptor interactions at different stages.

developmental biology↗

A novel and critical role of the intracellular Zona Pellucida protein 2 (ZP2) for blastocyst formation in mice

The zona pellucida (ZP) is the quintessential extracellular structure of mammalian oocytes. Contrary to long-standing view that the synthesis of ZP proteins is specific to oocytes and muted in embryos, we report here that the major zona pellucida protein ZP2 is re-synthesized and functionally required during mouse embryo development. The orthogonal methods of mass spectrometry and monoclonal immunofluorescence revealed an increase of ZP2 abundance at the 8-cell / morula stage, which did not occur when zygotes were microinjected with translation-blocking oligonucleotides (morpholinos). To shed light on the functional significance of embryonic ZP2, we performed protein knockdown using immunodepletion (by Trim-Away) while at the same time preventing replenishment (by translation-blocking morpholino). ZP2 knockdown resulted in morula stage retardation and formation of defective blastocysts, whose cell lineages trophectoderm and primitive endoderm were smaller and less able to support post-implantation development. The transcriptional correlates of these morphological alterations had a gene ontology (biological process) signature that included cell lineage-relevant terms ( endoderm development, gastrulation), while the proteomic correlates had a gene ontology signature related to protein synthesis. Taken together, these results call into question the traditional model that ZP proteins function solely in the extracellular space and accompany embryogenesis as passive bystanders: on the contrary, ZP proteins also participate actively in the intracellular processes of early embryogenesis.

developmental biology↗

Spatial and temporal requirement of Mlp60A isoforms during muscle development and function in Drosophila melanogaster

Many myofibrillar proteins undergo isoform switching in a spatio-temporal manner during muscle development. The biological significance of the variants of several of these myofibrillar proteins remains elusive. One such myofibrillar protein, the Muscle LIM Protein (MLP), is a vital component of the Z-discs. In this paper, we show that one of the Drosophila MLP encoding genes, Mlp60A, gives rise to two isoforms: a short (279 bp, 10 kDa) and a long (1461 bp, 54 kDa) one. The short isoform is expressed throughout development, but the long isoform is adult-specific, being the dominant of the two isoforms in the indirect flight muscles (IFMs). A concomitant, muscle-specific knockdown of both isoforms leads to late pupal lethality, with the surviving flies being majorly flight defective. Mlp60A null flies show developmental lethality, and muscle defects in the individuals surviving till the third instar larval stage. This lethality could be rescued partially by muscle-specific overexpression of the short isoform. Almost 90% of the long isoform-specific P-element insertion mutant flies show a compromised flight ability and have reduced sarcomere length. Hence, our data shows that the two Mlp60A isoforms are functionally specialized, to ensuring normal embryonic muscle development and adult flight muscle function.

developmental biology↗

GPX4-associated Sedaghatian Type Spondylometaphyseal Dysplasia: A Protein Interactome Perspective

Spondylometaphyseal dysplasia, Sedaghatian type (SMDS) is a rare and lethal skeletal dysplasia inherited in an autosomal recessive manner and caused by mutations in GPX4. In order to expand the functional landscape of this poorly studied disorder and accelerate the discovery of biologically insightful and clinically actionable targets, we constructed SMDS-centric and GPX4-centric protein-protein interaction (PPI) networks, augmented with novel protein interactors predicted by our HiPPIP algorithm. The SMDS-centric networks included those that showed the interconnections of GPX4 with other putative SMDS-associated genes and genes associated with other skeletal dysplasias. The GPX4-centric network showed the interconnections of GPX4 with genes whose perturbation has been known to affect GPX4 expression. We discovered that these networks either contained or were enriched with genes associated with specific SMDS pathophenotypes, tissue-naive/fetus-specific functional modules and genes showing elevated expression in brain and/or testis similar to GPX4. We identified 7 proteins as novel interactors of GPX4 (APBA3, EGR4, FUT5, GAMT, GTF2F1, MATK and ZNF197) and showed their potential biological relevance to GPX4 or SMDS. Comparative transcriptome analysis of expression profiles associated with chondroplasia and immune-osseous dysplasia versus drug-induced profiles revealed 11 drugs that targeted the neighborhood network of GPX4 and other putative SMDS-associated genes. Additionally, resveratrol, which is currently being tested against a skeletal dysplasia in a clinical trial, was identified as another potential candidate based on the proximity of its targets to GPX4.

developmental biology↗

Distinct Biological and Biomechanical Features in TMJ and Knee Cartilages

The temporomandibular joint (TMJ) and the knee joint are two of the most frequently used joints in the body, with the mandibular condylar cartilage (MCC) and the articular cartilage (AC) covering the joint bone surfaces, respectively. Compromised MCC functions lead to various temporomandibular disorders (TMD), including TMJ osteoarthritis (TMJ OA); however, the mechanisms governing MCC homeostasis and its biomechanical properties are still poorly understood. In this study, we comprehensively compared the biological and biomechanical features of the MCC and AC in mice. Histological analysis on P1, P21, 3-month, and 10-month mice revealed the most drastic structural differences between MCC and AC at occlusion establishment (P21), with MCC found to be more susceptible to age-associated cartilage degeneration. Immunostaining revealed differentially distributed cartilage extracellular matrix components in MCC and AC, including collagen type I, II, and X, and highly enriched expression of several key transcriptional factors at the posterior region of the MCC, including sex determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2), and scleraxis (SCX). The posterior MCC also houses a group of long-lasting, slow-proliferative cells, as evidenced by the BrdU/EdU incorporation assay, suggesting the presence of a potential stem/progenitor cell niche at the posterior TMJ. Unbiased nanoindentation analysis revealed distinct biomechanical features between these joint cartilages. MCC exhibits a significantly lower elastic modulus (EIT) than AC, with the highest EIT observed at the anterior TMJ, which is oppositely associated with the fibrous layer thickness, but positively correlated with the ratio of the collagen type X-positive matrix in the cartilaginous layer. Altogether, this study provides a basic understanding of the biological and biomechanical features of the cartilaginous tissues in two important joints, which may facilitate our understanding of the physiology in the TMJ and knee joint, and support the applications of mouse models to study TMJ dysfunctions.

developmental biology↗

Changing rounds into squares or combining stripes: Diversity and formation of checkerboard patterns in Eukaryotes

Important in many human artistic cultures, checkerboard patterns are rare in nature like many motifs based on squared geometry. Nevertheless, they are expected to be very detectable by the visual systems due to their periodic geometry and contrasted two-tone coloring, therefore potential specific biological functions are suspected. Here, thanks to a biological survey, we draw the first diversity landscape of eukaryotic species bearing checkerboard patterns, confirming their rarity but also their presence in extremely diverse clades. Then, we selected two genera, Sarcophaga flies and Fritillaria flowers, to perform in-depth pattern analyses allowing us to make strong hypotheses on the mechanisms producing these very peculiar patterns, as no morphogenetic process was known to generate checkerboards. Although they share a similar geometry, these two genera appear to produce checkerboards through very different ways, showing a convergence of shape but not of processes. Whereas the Fritillaria analysis points to a geometric constraining of a Turing-like pattern by the parallel network of veins, that of Sarcophaga suggest the reuse of developmental boundaries and right-left symmetry, together by the combination of vertical and horizontal stripes. Furthermore, we present the first description to our knowledge of the striking color-changing nature of Sarcophaga checkerboards, whose light and dark squares can exchange their color depending on the angles of lighting and observation thanks to the planar polarity of the cuticular hairs, the setae. Together, this shows the extent of the processes selected during evolution to generate complex forms and colors, and confirms the importance of studying morphogenesis with in-depth pattern analyses and through species diversity. Finally, by enabling strong hypotheses to be made about the morphogenesis of these patterns, it paves the way for the molecular identification of the morphogenetic processes at work.

developmental biology↗

Material Properties Of The Embryonic Small Intestine During Buckling Morphogenesis

During embryonic development, tissues undergo dramatic deformations as functional morphologies are stereotypically sculpted from simple rudiments. Formation of healthy, functional organs therefore requires tight control over the material properties of embryonic tissues during development, yet the biological basis of embryonic tissue mechanics is poorly understood. The present study investigates the mechanics of the embryonic small intestine, a tissue that is compactly organized in the body cavity by a mechanical instability during development, wherein differential elongation rates between the intestinal tube and its attached mesentery create compressive forces that buckle the tube into loops with wavelength and curvature that are tightly conserved for a given species. Focusing on the intestinal tube, we combined micromechanical testing with histologic analyses and enzymatic degradation experiments to conclude that elastic fibers closely associated with intestinal smooth muscle layers are responsible for the bending stiffness of the tube, and for establishing its pronounced mechanical anisotropy. These findings provide insights into the developmental role of elastic fibers in controlling tissue stiffness, and raise new questions on the physiologic function of elastic fibers in the intestine during adulthood. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/606927v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1bbf9d9org.highwire.dtl.DTLVardef@10428eorg.highwire.dtl.DTLVardef@181b530org.highwire.dtl.DTLVardef@9e758c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗