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Results for “developmental biology”

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bioRxiv2020

The 3UTR of the orb2 gene encoding the Drosophila CPEB translation factor plays a critical role in spermatogenesis

CPEB proteins are conserved translation regulators involved in multiple biological processes. One of these proteins in Drosophila, Orb2, is a principal player in spermatogenesis. It is required for meiosis and spermatid differentiation. During the later process orb2 mRNAs and proteins are localized within the developing spermatid. To evaluate the role of orb2 mRNA 3UTR in spermatogenesis, we used the CRISPR/Cas9 system to generate a deletion of the orb2 3UTR, orb2R. This deletion disrupts the process of spermatid differentiation, but has no apparent effect on meiosis. While this deletion appears to destabilize the orb2 mRNA and reduce the levels of Orb2 protein, this is not the primary cause of the differentiation defects. Instead, differentiation appears to be disrupted because orb2 mRNAs and proteins are not properly localized within the differentiating spermatids. Other transcripts and proteins involved in spermatogenesis are also mislocalized in orb2R spermatids. Author summaryThe conserved family of cytoplasmic polyadenylation element binding (CPEB) proteins can activate or repress translation of target mRNAs, depending on the specific biological context, through interaction with special cytoplasmic polyadenylation element (CPE) sequences. These proteins function mainly in highly polarized cells. Orb2, one of the two Drosophila melanogaster CPEB proteins, is predominantly expressed in the testes and is crucial for spermatogenesis. The 3UTR of orb2 transcript contains multiple CPE-like motifs, which is indicative of orb2 self-regulation. We have generated a deletion that removes the greater portion of 3UTR. While this deletion causes a reduction in the levels of orb2 mRNA and the protein, this does not appear to be responsible for the defects in spermatogenesis observed in the deletion mutant. Instead, it is the mislocalization of the mRNA and protein in the developing spermatids.

developmental biology↗

bioRxiv2021

DDX41 is needed for pre-and post-natal hematopoietic stem cell differentiation in mice

DDX41 is a tumor suppressor frequently mutated in human myeloid neoplasms. DDX41 binds to DNA/RNA hybrids and interacts with spliceosome component (1, 2). How it affects hematopoiesis is still unclear. Using a knockout mouse model, we demonstrate that DDX41 is required for mouse hematopoietic stem and progenitor cell (HSPC) survival and differentiation. Lack of DDX41 particularly affected myeloid progenitor development, starting at embryonic day 13.5. DDX41-deficient fetal liver and adult bone marrow (BM) cells were unable to rescue mice from lethal irradiation after transplantation. DDX41 knockout stem cells were also defective in ex vivo colony forming assays. RNASeq analysis of lineage-negative, cKit+Sca1+ cells isolated from fetal liver demonstrated that the expression of many genes associated with hematopoietic differentiation were altered in DDX41 knockout cells. Furthermore, altered splicing of genes involved in key biological processes were observed. Our data reveal a critical role for DDX41 in HSPC differentiation and myeloid progenitor development, likely through its regulation of gene expression programs and splicing. SignificanceDDX41 is a tumor suppressor in hematologic malignancies. However, whether DDX41 functions in hematopoiesis and myeloid cell differentiation is not known. Here we show that in mice, loss of DDX41 in hematopoietic stem cells (HSCs) leads to defects in hematopoietic development. The myeloid lineage was particularly affected as early as pre-natal stages. Transcriptional profiling of embryonic HSCs revealed that there were global changes in gene expression and splicing due to lack of DDX41. Collectively, the study uncovers a new function of DDX41 in HSC differentiation and could provide molecular targets for treatment of myeloid differentiation disorders.

developmental biology↗

bioRxiv2025

Modeling tissue-resident macrophage development from mouse pluripotent stem cells

Tissue-resident macrophages (TRMs) are innate immune cells that participate in tissue development, homeostasis, and immune surveillance. Extensive efforts have been made to recapitulate TRM development from pluripotent stem cells (PSCs) in vitro to study molecular and cellular mechanisms of TRM development and to create cellular models of disease. However, available PSC models of mouse TRM development exhibit low overall efficiencies of TRM generation, produce heterogeneous off-target populations, and rely upon undefined media components, thus limiting their reproducibility, scalability, and widespread application as an experimental platform for TRM biology. To address these important limitations, we developed an efficient and reproducible protocol to faithfully recapitulate the stepwise differentiation of mouse PSCs (epiblast stem cells) into unspecialized, proliferative TRMs through the pro-definitive hematopoietic program under defined conditions. These immature TRMs can stably integrate into developing mouse neural organoids in vitro and acquire features of microglia. In addition, PSC-derived immature TRMs can stably engraft into the lung niche in vivo and adopt alveolar macrophage characteristics. This new platform for modeling mouse TRM development represents a powerful experimental model system for studying TRM function and dysfunction in development and disease.

developmental biology↗

bioRxiv2017

PolNet Analysis: a software tool for the quantification of network-level endothelial cell polarity and blood flow during vascular remodelling

In this paper, we present PolNet, an open source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterise the haemodynamics of the vascular networks under study. The tool enables, for the first time, network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarisation and migration during vascular patterning, as demonstrated by our recent papers [1, 2]. Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the LGPL licence.

developmental biology↗

bioRxiv2023

Maternal regulation of the vertebrate egg-to-embryo transition

Egg activation and early embryonic development are complex and highly regulated processes that involve a series of coordinated cellular and molecular events after fertilization. While significant progress has been made in unraveling the mechanisms underlying these processes, there remains a need to comprehensively understand the precise molecular pathways and regulatory factors involved. We characterized four recessive maternal-effect mutants identified from a zebrafish forward genetic screen that function during the egg-to-embryo transition. We found that these genes encompass distinct aspects of egg activation, including cortical granule biology, cytoplasmic segregation, and the suppression of microtubule organizing center (MTOC) assembly and ectopic aster-like microtubule formation. These genes are essential to the development of the early embryo and the establishment of the basic body plan. Notably, we discovered a novel gene that we named krang, which is highly conserved across metazoans. Maternal Krang was found to be associated with the function of cortical granules during egg activation. This collection of mutants represents valuable tools to understand the genetic architecture underlying phenotypic traits shaping the egg-to-embryo transition. Furthermore, these results highlight the evolutionary conservation of maternal functions in diverse species. By deepening our understanding of these findings, we will improve our knowledge of reproductive traits and potentially develop new diagnostic tools to address human reproductive disorders. Author SummaryDuring egg activation, the egg undergoes a series of biochemical and cellular modifications that activate its dormant metabolism, preparing it to initiate embryonic development. Egg activation initiates the completion of meiosis, and the newly formed zygote undergoes a series of additional changes, including the cell cycle establishment. However, our knowledge of the molecular mechanisms controlling these processes remain limited. We identified four recessive maternal-effect mutants in zebrafish that exhibit a range of developmental alterations during egg activation and early embryogenesis. We found that these maternally acting mutant genes are associated with defects in cortical granule exocytosis, yolk-cytoplasm segregation, microtubule nucleation and dynamics that are critical for the egg-to-embryo transition. Our results suggest that the proper regulation of these processes is essential for successful egg development and embryogenesis. We characterized the Krang factor, which regulates aspects of egg activation likely by modulating the secretory pathway. Further studies on this gene may provide new insights into the molecular mechanisms underlying oocyte development and egg quality acquisition. Overall, our collection of maternal-effect mutants sheds light on the proper regulation of key molecular and cellular events for successful egg development, with important implications for reproductive medicine and assisted reproductive technologies.

developmental biology↗

bioRxiv2020

The C. elegans proteasome subunit RPN-12 is required for hermaphrodite germline sex determination and oocyte quality

BackgroundThe proteasome is a multi-subunit complex and a major proteolytic machinery in cells. Most subunits are essential for proteasome function, and depletion of individual subunits normally results in lethality. RPN-12/Rpn12/PSMD8 is a lid subunit of the 19S regulatory particle (RP) of the 26S proteasome. Studies in Caenorhabditis elegans demonstrated that RNAi depletion of RPN-12 does not result in lethality. RPN-12 has not been well studied in higher eukaryotes. In this study we investigate the biological significance of RPN-12 in C. elegans. ResultsWe found that the null mutant rpn-12(av93) did not cause major impairment of the proteolytic activity of the proteasome. Most rpn-12(av93) hermaphrodites lack sperm leading to feminization of the germ line that can be partially rescued by mating to males. The lack of sperm phenotype can be suppressed by downregulation of TRA-1, a player in the hermaphrodite germline sex determination pathway. Also, rpn-12(av93) animals show significant nuclear accumulation of the meiotic kinase WEE-1.3, a protein predominantly localized to the perinuclear region. Interestingly, chemical inhibition of the proteasome did not cause nuclear accumulation of WEE-1.3. ConclusionsRPN-12 plays a previously unknown role in oogenesis and the germline sex determination pathway in C. elegans hermaphrodites.

developmental biology↗

bioRxiv2018

Chronic estrus disrupts uterine gland development and homeostasis

Female mice homozygous for an engineered Gnrhr E90K mutation have reduced gonadotropin-releasing hormone signaling, leading to infertility. Their ovaries have numerous antral follicles but no corpora lutea, indicating a block to ovulation. These mutants have high levels of circulating estradiol and low progesterone, indicating a state of persistent estrus. This mouse model provided a unique opportunity to examine the lack of cyclic levels of ovarian hormones on uterine gland biology. Although uterine gland development appeared similar to controls during prepubertal development, it was compromised during adolescence in the mutants. By 20 weeks of age, uterine gland development was comparable to controls, but pathologies, including squamous neoplasia, tubal neoplasia, and cribriform glandular structures, were observed. Induction of ovulations by periodic human chorionic gonadotropin treatment did not rescue post-pubertal uterine gland development. Interestingly, progesterone receptor knockout mice, which lack progesterone signaling, also have defects in post-pubertal uterine gland development. However, progesterone treatment did not rescue post-pubertal uterine gland development. These studies indicate that chronically elevated levels of estradiol with low progesterone and therefore an absence of cyclic ovarian hormone secretion disrupts post-pubertal uterine gland development and homeostasis.

developmental biology↗

bioRxiv2020

Simulating flow induced migration in vascular remodelling

Shear stress induces directed endothelial cell (EC) migration in blood vessels leading to vessel diameter increase and induction of vascular maturation. Other factors, such as EC elongation and interaction between ECs and non-vascular areas are also important. Computational models have previously been used to study collective cell migration. These models can be used to predict EC migration and its effect on vascular remodelling during embryogenesis. We combined live time-lapse imaging of the remodelling vasculature of the quail embryo yolk sac with flow quantification using a combination of micro-Particle Image Velocimetry and computational fluid dynamics. We then used the flow and remodelling data to inform a model of EC migration during remodelling. To obtain the relation between shear stress and velocity in vitro for EC cells, we developed a flow chamber to assess how confluent sheets of ECs migrate in response to shear stress. Using these data as an input, we developed a multiphase, self-propelled particles (SPP) model where individual agents are driven to migrate based on the level of shear stress while maintaining appropriate spatial relationship to nearby agents. These agents elongate, interact with each other, and with avascular agents at each time-step of the model. We compared predicted vascular shape to real vascular shape after 4 hours from our time-lapse movies and performed sensitivity analysis on the various model parameters. Our model shows that shear stress has the largest effect on the remodelling process. Importantly, however, elongation played an especially important part in remodelling. This model provides a powerful tool to study the input of different biological processes on remodelling. Author summaryShear stress is known to play a leading role in endothelial cell (EC) migration and hence, vascular remodelling. Vascular remodelling is, however, more complicated than only EC migration. To achieve a better understanding of this process, we developed a computational model in which, shear stress mediated EC migration has the leading role and other factors, such as avascular regions and EC elongation, are also accounted for. We have tested this model for different vessel shapes during remodelling and could study the role that each of these factors play in remodelling. This model gives us the possibility of addition of other factors such as biochemical signals and angiogenesis which will help us in the study of vascular remodelling in both development and disease.

developmental biology↗

bioRxiv2025

Cilia.io: Computer vision and machine learning reveal spatial patterns of cilia beating dynamics in the spinal cord

Motile cilia coordinate fluid flows that are essential for normal tissue physiology and function. Cilia display diverse beating waveforms, and while pronounced defects are strongly associated with motile ciliopathies, more subtle alterations may also influence disease manifestations. Finer quantification of ciliary dynamics is critical for a full understanding of cilia-associated disorders, but the heterogeneity of cilia beating dynamics makes accurate and robust characterization challenging. Because existing tools have proven to be limiting in noisy in vivo environments, we developed Cilia.io, a machine learning (ML)-based quantification tool that uses state-of-the-art vision transformers to segment cilia out of the background based on their biological features. Cilia.io enables fast, accurate, and reproducible quantification of motile cilia morphodynamics and outperforms existing tools. Indeed, using Cilia.io, we discovered distinct regional differences in ciliary waveforms in the zebrafish spinal cord. The ability of Cilia.io to capture subtle ciliary defects was further demonstrated by analyzing a novel allele in the ciliopathy gene bbs2 that causes a highly heterogeneous scoliosis phenotype. In these mutants, only dorsal cilia displayed altered beating dynamics, while ventral cilia remained largely unaffected. Our new tool therefore represents a substantial advance on existing methods and suggests that additional fine-scale analyses of ciliary beating will be important for understanding organismal phenotypes and cilia-driven disease.

developmental biology↗

bioRxiv2020

The number of growing microtubules and nucleus-nucleus interactions uniquely regulate nuclear movement in Drosophila muscle

Nuclear movement is a fundamental process of eukaryotic cell biology. Skeletal muscle presents an intriguing model to study nuclear movement because its development requires the precise positioning of multiple nuclei within a single cytoplasm. Furthermore, there is a high correlation between aberrant nuclear positioning and poor muscle function. Although many genes that regulate nuclear movement have been identified, the mechanisms by which these genes act is not known. Using Drosophila melanogaster muscle development as a model system, and a combination of live-embryo microscopy and laser ablation of nuclei, we have found that phenotypically similar mutants are based in different molecular disruptions. Specifically, ensconsin (Drosophila MAP7) regulates the number of growing microtubules that are used to move nuclei whereas bocksbeutel (Drosophila emerin) and klarsicht (Drosophila KASH-protein regulate interactions between nuclei.

developmental biology↗

bioRxiv2024

A Deep Learning Model for Accurate Segmentation of the Drosophila melanogaster Brain from Micro-CT Imaging

The use of microcomputed tomography (Micro-CT) for imaging biological samples has burgeoned in the past decade, due to increased access to scanning platforms, ease of operation, isotropic three-dimensional image information, and the ability to derive accurate quantitative data. However, manual data analysis of Micro-CT images can be laborious and time intensive. Deep learning offers the ability to streamline this process, but historically has included caveats--namely, the need for a large amount of training data, which is often limited in many Micro-CT studies. Here we show that accurate deep learning models can be trained using only 1-3 Micro-CT images of the adult Drosophila melanogaster brain using Dragonflys pre-trained neural networks and minimal user knowledge. We further demonstrate the power of our model by showing that it can accurately segment the brain across different tissue contrast stains, scanner models, and genotypes. Finally, we show how the model can assist in identifying morphological similarities and differences between mutants based on volumetric quantification, facilitating a rapid assessment of novel phenotypes. Our models are freely available and can be refined based on individual user needs. SummaryMicro-CT data can be automatically segmented and quantified using a deep learning model trained on as few as 3 samples, facilitating rapid comparison of developmental phenotypes.

developmental biology↗

bioRxiv2026

Specification of bone marrow sinusoids requires TIE2-mediated positive feedback involving COUPTFII and VEGFR3

The bone marrow (BM) vascular network plays crucial roles in driving bone development and supporting hematopoiesis, yet the mechanisms governing its specialized architecture, particularly sinusoidal morphogenesis, remain inadequately characterized. We show in this study that TIE2 (Tek) was highly expressed by BM sinusoidal endothelial cells (SEC) and the endothelial Tek excision led to BM sinusoidal capillarization. Particularly, the BM sinusoids displayed thinner vessel diameter with the aberrant mural cell coverage in the Tek mutants. Mechanistically, TIE2 insufficiency led to a dramatic decrease of VEGFR3 in BM-SECs while its expression in hepatic sinusoids was not obviously altered. The RNA-seq analysis showed that GO terms enriched for the downregulated genes were related to the biological processes including sinusoidal development while pathways related to arterial ECs and angiogenesis were upregulated in the bone marrow of Tek mutants. The alteration of sinusoidal VEGFR3 expression occurred within 48 h after the induced endothelial deletion of Tek. Consistently, the defective BM sinusoidal formation was validated with the induced Tek deletion in VEGFR3+ SECs. The insufficiency of TIE2 ligand ANGPT1 also led to reduced sinusoidal VEGFR3, accompanied by similar BM sinusoidal defects. Furthermore, disruption of sinusoidal morphogenesis was observed in mutant mice with the endothelial excision of Nr2f2 (COUP-TFII), displaying a decreased expression of BM sinusoidal TIE2 and VEGFR3. These findings suggest that ANGPT1/TIE2 and COUP-TFII form a reciprocal regulatory loop to coordinate BM sinusoidal specification via regulating VEGFR3.

developmental biology↗

bioRxiv2020

Rcn3 is Involved in Postnatal Tendon Development by Regulating Collagen Modification and Fibrillogenesis

Tendon plays a critical role in the joint movement by transmitting force from muscle to bone. This transmission of force is facilitated by its specialized structure, which consists of highly aligned extracellular matrix consisting predominantly of type I collagen. Tenocytes, fibroblast-like tendon cells residing between the parallel collagen fibers, regulate this specialized tendon matrix. Despite the importance of collagen structure and tenocyte function, the biological mechanisms regulating fibrillogenesis and tenocyte maturation are not well understood. Here we examine the function of Reticulocalbin 3 (Rcn3) in collagen fibrillogenesis and tenocyte maturation during postnatal tendon development using a genetic mouse model. Loss of Rcn3 in tendon caused decreased tendon thickness, abnormal tendon cell maturation, and decreased mechanical properties. Interestingly, Rcn3 deficient mice exhibited a smaller collagen fibril distribution and over-hydroxylation in C-telopeptide cross-linking lysine from 1(1) chain. Additionally, the proline 3-hydroxylation sites in type I collagen were also over-hydroxylated in Rcn3 deficient mice. Our data collectively suggest that Rcn3 is a pivotal regulator of collagen fibrillogenesis and tenocyte maturation during postnatal tendon development.

developmental biology↗

bioRxiv2022

Dynamic chromatin organization and regulatory interactions in human endothelial cell differentiation

BackgroundVascular endothelial cells are a mesoderm-derived lineage with many essential functions, including angiogenesis and coagulation. However, the gene regulatory mechanisms that underpin endothelial specialization are largely unknown, as are the roles of 3D chromatin organization in regulating endothelial cell transcription. MethodsTo investigate the relationships between 3D chromatin organization and gene expression in endothelial cell differentiation, we induced endothelial cell differentiation from human pluripotent stem cells and performed Hi-C and RNA-seq assays at specific timepoints in differentiation. ResultsOur analyses reveal that long-range intrachromosomal contacts increase over the course of endothelial cell differentiation, as do genomic compartment transitions between active and inactive states. These compartmental states are tightly associated with endothelial transcription. Dynamic topologically associating domain (TAD) boundaries strengthen and converge on an endothelial cell state, and nascent TAD boundaries are linked to the expression of genes that support endothelial cell specification. Relatedly, chromatin pairwise point interactions (DNA loops) increase in frequency during differentiation and are linked to the expression of genes with essential roles in vascular biology, including MECOM, TFPI, and KDR. To identify forms of regulation specific to endothelial cell differentiation, we compared the functional chromatin dynamics of endothelial cells with those of developing cardiomyocytes. Cardiomyocytes exhibit greater long-range cis interactions than endothelial cells, whereas endothelial cells have increased local intra-TAD interactions and much more abundant pairwise point interactions. ConclusionsGenome topology changes dynamically during endothelial differentiation, including acquisition of long-range cis interactions and new TAD boundaries, interconversion of hetero- and euchromatin, and formation of DNA loops. These chromatin dynamics guide transcription in the development of endothelial cells and promote the divergence of endothelial cells from related cell types such as cardiomyocytes.

developmental biology↗

bioRxiv2026

Exploration of the screening and regulatory mechanisms of biomarkers related to ac4C modification in laryngeal squamous cell carcinoma patients based on single-cell analysis and machine learning

BackgroundN4-acetylcytidine (ac4C) modification plays a critical role in cancer development. Exploring ac4C modification in laryngeal squamous cell carcinoma (LSCC) may help elucidate its pathogenesis. MethodsLSCC-related datasets were obtained from GEO. After preprocessing and annotating single-cell data, malignant cells were identified by CNV scoring and further divided into subpopulations. Malignant epithelial cells (MECs) were identified and subclustered based on ac4C-related gene activity. Prognostic genes were screened using Cox regression and machine-learning approaches, followed by validation in clinical samples using qPCR. The biological and immunological relevance of these genes was further explored through immune infiltration, immunotherapy response, and mutation analyses. ResultsThe 14,465 identified MECs were classified into five subgroups (MEC1-5), among which MEC3 showed the strongest association with the ac4C gene set. Machine-learning analysis of MEC3-derived genes yielded seven prognostic markers, including BARX1, FHL2, NXPH4, PKMYT1, TNFAIP8L1, CRLF1, and CENPP. qPCR confirmed their differential expression between tumor and adjacent normal tissues. These genes were significantly associated with alterations in the tumor immune microenvironment, with high-risk patients showing increased immune infiltration and immune activity. ConclusionSeven ac4C-related prognostic genes were identified that may contribute to LSCC progression by modulating the tumor immune microenvironment, providing potential therapeutic insights.

developmental biology↗

bioRxiv2024

Fibroblast diversification is an embryonic process dependent on muscle contraction

Fibroblasts are the most common cell type found in connective tissues, known to play major roles in development, homeostasis, regeneration and disease. Although specific fibroblast subpopulations were associated with different biological processes, the mechanisms and unique activities underlying their diversity has not been thoroughly examined. Turning to skeletal muscle development, we set to dissect the variation of muscle-resident fibroblasts (mrFibroblasts). Our results demonstrate mrFibroblasts diversify following the transition from embryonic to fetal myogenesis prior to birth. We find mrFibroblast segregate into two major subpopulations occupying distinct niches, with interstitial fibroblasts residing between the muscle fibers, and delineating fibroblasts sheathing the muscle mass. We further show these subpopulations entail distinct cellular dynamics and transcriptomes. Notably, we find mrFibroblast subpopulations exert distinct regulatory roles on myoblast proliferation and differentiation. Finally, we demonstrate this diversification depends on muscle contraction. Altogether, these findings establish mrFibroblast diversify in a spatio-temporal embryonic process into distinct cell types, entailing different characteristics and roles.

developmental biology↗

bioRxiv2025

SLC35G3 is a UDP-N-acetylglucosamine transporter for sperm glycoprotein formation and underpins male fertility in mice

Despite the recognized importance of glycans in biological phenomena, their complex roles in spermatogenesis and sperm function remain unclear. SLC35G3, a 10-transmembrane protein specifically found in early round spermatids, belongs to the sugar-nucleotide transporter family, indicating its involvement in glycan formation. In this study, we found that Slc35g3 knockout male mice were sterile due to impaired sperm functions in uterotubal junction passage, zona pellucida binding, and oocyte fusion. Mouse SLC35G3 has UDP-GlcNAc transporter activity, and its ablation caused abnormal processing of the sperm plasma membrane and acrosome membrane proteins. Reported human SLC35G3 mutations (F267L and T179HfsTer27) diminished the UDP-GlcNAc transporter activity of SLC35G3, implying infertility risks in males carrying these mutations. Our findings unveil the vital roles of SLC35G3 in the glycan formation of sperm membrane proteins critical for sperm fertilizing ability.

developmental biology↗

bioRxiv2022

Zebrafish cornea formation and homeostasis reflect robustness in camera-type eye biology, regardless of its environment

The cornea is the transparent tissue covering the camera-type eyes. This position makes this tissue prone to environmental aggressions, and physical alteration can have a drastic negative impact on sight. The current knowledge on zebrafish corneal physiology is too scarce to get an understanding on its strategy to maintain a clear sight in aquatic environment. In this study, we focus on corneal formation and maturation in zebrafish. After describing the morphological changes taking place from 3 days post fertilization to adulthood, we analyzed cell proliferation. We show that label retaining cells appear just before 1 month of age. Our cell proliferation study, combined to the study of Pax6a and krtt1c19e expression, demonstrate a long maturation process. This process ends with a solid patterning of corneal innervation. Finally, corneal abrasion wound healing process recapitulates the maturation process, via a plasticity period. Altogether, our study decipher the maturation steps of an aquatic cornea. These findings will facilitate the use of zebrafish as model of corneal physiology studies.

developmental biology↗