Journal of Developmental Biology最新文献

Craniofacial development is orchestrated by a finely regulated interplay of numerous genes and signaling pathways. Palatogenesis proceeds through a complex, stepwise process, in which endogenous mechanical stresses within tissues have been implicated. However, the impact of exogenous fluidic flow mechanical stress derived from maternal movement on palatal development remains unclear. In this study, we investigated the effect of exogenous fluidic flow mechanical stress on palatal morphogenesis, focusing on the horizontal outgrowth of palatal shelves after elevation. Palatal tissues dissected from mouse embryos were subjected to organ culture with or without mechanical loading (loaded and unloaded groups, respectively). Stress magnitude was quantified by calculating wave energy, and morphometric and molecular analyses were performed. Compared with the unloaded group, palatal shelves in the loaded group showed significant increases in thickness and volume, accompanied by enhanced cell proliferation, nuclear translocation of YAP and β-catenin, and upregulation of the osteogenic markers Osterix and Osteocalcin. No significant difference in apoptosis was observed. These findings indicate that exogenous mechanical stress promotes cell proliferation and osteogenic differentiation through the Hippo and WNT/β-catenin pathways in palate explants. Our results suggest that moderate maternal movement-induced mechanical stress contributes to normal palatogenesis, providing new insights into the mechanisms underlying cleft palate.

VESTIGIAL-LIKE proteins constitute a family of evolutionarily conserved proteins that act as cofactors in regulating gene expression through their binding to TEAD transcription factors. Among the four members of this family in vertebrates, VESTIGIAL-LIKE 4 has emerged as a tumor suppressor that competes with YAP in binding TEADs, thus inhibiting the HIPPO pathway downstream of YAP. Nevertheless, very few studies have addressed its function during early vertebrate development. Here, we used gain- and loss-of-function strategies to investigate the role of vestigial-like 4 during Xenopus laevis development. Our data show that vestigial-like 4 is a key regulator of neurogenesis and neural crest formation. In embryos depleted of vestigial-like 4, neurogenesis is severely impaired, and neither neurog1 nor neurod1 is able to stimulate neurogenesis. Vestigial-like 4 is also required for neural crest formation through pax3 and sox9 regulation, and this property does not necessarily require its interaction with tead. Collectively, our findings demonstrate that vestigial-like 4 is an important regulator of neurogenesis and neural crest formation. Although vestigial-like 4 can bind to tead proteins in the embryo, its function does not depend solely on this interaction, suggesting a complex level of regulation with which vestigial-like 4 regulates early steps in development and differentiation.

Lampbrush chromosomes (LBCs) are a feature of amphibian oocytes and are typically associated with high levels of transcription during active oocyte growth. However, their state during winter hibernation has not been studied. Here, we investigated LBCs in early vitellogenic oocytes (early stage 4) of the grass frog Rana temporaria during winter hibernation. We found that the chromosomes retained their lampbrush morphology, and the phosphorylated form of RNA polymerase II resided on the lateral loops. Transcription on the lateral loops was reduced but detectable at cold conditions and significantly increased when the oocytes were transferred at room temperature. Satellite S1a transcripts were detected at the lateral loops of the chromosomes by RNA FISH. The possible significance of maintaining chromosomes in the lampbrush form during hibernation is discussed.

Cumulus cells (CCs) are a distinct population of granulosa cells (GCs) that surround the developing and ovulated mammalian oocyte. The features of their structural organization and the expression pattern of key genes significantly affect oocyte viability. Changes in the functional activity of the nucleus are often expressed in changes in the structure of nuclear bodies (NBs), including Cajal bodies (CBs). The diagnostic protein of CBs is coilin, which maintains their structural integrity. Using fluorescent and electron microscopy, we examined maternal aging-associated changes in coilin pattern in mouse CCs. We found that older mice had a decrease in the number of coilin-positive bodies, while external transcriptome data analysis revealed no significant changes in Coil and Smn1 gene expression. We hypothesized that the age-related dynamics of coilin-containing bodies are determined not by changes in the expression level of key components of these bodies, but by age-related changes in CC metabolism. Considering that CCs are a by-product of IVF protocols, making them available for analysis in sufficient quantities, age-related changes in the number and size of coilin-positive NBs in CCs may serve as a promising biomarker for assessing ovarian functional aging.

Obstructive uropathy (OU) during fetal development induces a fetal cystic dysplastic kidney. The mechanisms of cyst formation and the onset of renal dysfunction remain unclear. Determining whether nephrogenic potential persists during fetal life may suggest whether early intervention could preserve renal development. We aimed to evaluate residual nephrogenic activity in fetal cystic dysplastic kidneys using β-catenin and CD10 immunostaining, and to assess whether the site of obstruction influences cystogenesis. After appropriate approval, 20 timed-gestation fetal lambs had OU created at 60 days. Males underwent urethral and urachal ligation (n = 8, 3 lost), and females underwent unilateral ureteric ligation (n = 8, 1 lost). Fetuses were sacrificed at 80 days (n = 6) and 140 days (term, n = 10), comparing kidneys with normal controls of the same gestational age using immunohistochemical staining for β-catenin and CD10. Developing fetal cystic dysplastic kidneys were identified at 80 days. β-catenin staining showed the absence of granular cytoplasmic expression in cystic regions, indicating arrested nephrogenesis. In male models, cysts originated exclusively from proximal tubules. Female models exhibited mixed proximal and distal tubular involvement. CD10 staining confirmed the loss of proximal tubular markers. Renal development remained arrested at term. Cyst formation disrupts renal development early in gestation, which persists until term. Differences in cystogenesis between the models suggest that the site of obstruction influences pathogenic mechanisms.

Erythro-myeloid progenitors (EMPs) originate from the haemogenic endothelium in the yolk sac via an endothelial-to-haematopoietic transition (EHT) to generate blood and immune cells that support embryo development. Yet, the transitory nature of EHT and the limited availability of molecular markers have constrained our understanding of the origin, identity, and differentiation dynamics of EMPs. Here, we have refined the annotation of yolk sac haemato-vascular populations in publicly available single-cell RNA sequencing (scRNAseq) datasets from mouse embryos to identify novel molecular markers of haemogenic endothelium and EMPs. By sub-clustering key cell populations followed by pseudotime analysis, we refined cluster annotations and then reconstructed differentiation trajectories. Subsequent differential gene expression analysis between clusters identified novel cell surface markers for haemogenic endothelial cells (Fxyd5 and Scarf1) and EMPs (Fcer1g, Tyrobp, and Mctp1). Further, we have identified candidate signalling and metabolic pathways that may regulate yolk sac haematopoietic emergence and differentiation. The specificity of FXYD5, SCARF1, and FCER1G for haemogenic endothelium and EMPs was validated by immunostaining of the mouse yolk sac. These insights into the transcriptional dynamics in the yolk sac should support future investigation of EHT and haematopoietic differentiation during early mammalian development.

Maternal nutrition during gestation profoundly influences fetal growth, organogenesis, and long-term offspring performance through developmental programming. Among the molecular mechanisms responsive to maternal nutrient availability, one-carbon metabolism plays a central role by integrating folate, methionine, choline, and vitamin B₁₂ pathways that regulate methylation, nucleotide synthesis, and antioxidant defense. These processes link maternal nutritional status to epigenetic remodeling, cellular proliferation, and redox balance during fetal development. Mitochondria act as nutrient sensors that translate maternal metabolic cues into bioenergetic and oxidative signals, shaping tissue differentiation and metabolic flexibility. Variations in maternal diet have been associated with shifts in fetal amino acid, lipid, and energy metabolism, suggesting adaptive responses to constrained intrauterine environments. This review focuses on the molecular interplay between one-carbon metabolism, mitochondrial function, and metabolomic adaptation in developmental programming of ruminant livestock. Understanding these mechanisms offers opportunities to design precision nutritional strategies that enhance fetal growth, offspring productivity, and long-term resilience in livestock production systems.

Mutations in the transcriptional co-factor HCFC1 cause methylmalonic aciduria and homocystinemia, cblX type (cblX) (MIM#309541), non-syndromic X-linked intellectual disability (XLID), and focal epilepsy. Zebrafish studies have revealed increased activation of the Akt/mTor signaling pathway after mutation of hcfc1a, one ortholog of HCFC1. mTOR hyperactivation is linked to seizures, and its inhibition alleviates epilepsy in other preclinical models. We hypothesized that mTor overactivity in hcfc1a mutant zebrafish increases seizure susceptibility and/or severity. We employed a two-concentration model of the seizure-inducing agent, pentylenetetrazol (PTZ), with or without pretreatment of the mTor inhibitor, torin1. Mutation of hcfc1a did not alter the response to PTZ at sub-optimal concentrations, and the pharmaceutical inhibition of mTor using the compound Torin1 reduced response to 1 µM PTZ, but only in a dose-dependent manner. Higher doses of mTor inhibition did not reduce the seizure response in mutant larvae but were effective in wildtype siblings. These data suggest that inhibition of mTor in an hcfc1a-deficient background leads to a reaction that differs from the traditional response observed in wildtype siblings. Collectively, we present a model that can be used to test dose-response and the development of combinatorial treatment approaches in a high-throughput manner.

The epithelial egg tooth is used by birds to open the eggshell for hatching. This ectodermal structure consists of a multilayered periderm and a hard cornified portion, the caruncle or actual egg tooth. Here, we determined the protein composition of the egg tooth of the chicken and compared the proteins to markers of other epithelia identified in previous studies. The egg tooth and the upper beak of chicken embryos of Hamburger and Hamilton (HH) stage 44 were subjected to mass spectrometry-based proteomics. We found that scaffoldin, a marker of the embryonic periderm and the feather sheath, was enriched in the egg tooth relative to the beak. Likewise, Epidermal Differentiation protein containing DPCC Motifs (EDDM) and Epidermal Differentiation protein starting with a MTF motif and rich in Histidine (EDMTFH), which had previously been characterized as markers of the subperiderm on embryonic scutate scales and the barbs of feathers, were also enriched in the egg tooth. The expression of EDDM and EDMTFH was confirmed RT-PCR analysis. Our data suggest that the epithelial egg tooth is related to the subperiderm and feathers, a hypothesis with potentially important implications for the evolution of the avian integument.

Placenta Accreta Spectrum (PAS) disorders, including placenta accreta, increta, and percreta, are serious obstetric conditions characterized by abnormal placental adherence to the uterine wall. With increasing incidence, PAS poses significant risks, primarily through massive hemorrhage during or after delivery, often necessitating hysterectomy. Key risk factors include prior cesarean sections, uterine surgery, and placenta previa diagnosis. In this review, we will examine the pathophysiology of PAS, with a focus on the mechanisms underlying abnormal trophoblast invasion and defective decidualization. We will highlight the role of uterine scarring, extracellular matrix remodeling, dysregulated signaling pathways, and immune and vascular alterations in disrupting the maternal-fetal interface, ultimately predisposing to morbid placentation and delivery complications. We will also discuss the life-threatening complications of PAS, such as shock and multi-organ failure, which require urgent multidisciplinary intensive care, as well as the optimization of management through preoperative planning and intraoperative blood loss control to reduce maternal morbidity and mortality.