The International Journal Of Developmental Biology[JOURNAL]
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200 papers
Prenatal alcohol exposure affects developmental differentiation of interictal discharges in septal and temporal hippocampus.
Evangelaki ME, Psarropoulou C
Int J Dev Biol · 2022 · PMID 34881801 · Publisher ↗
Prenatal alcohol exposure (PAE) provokes lifelong CNS dysfunction, including an increased susceptibility to seizure disorders. We investigated hippocampal excitability in the offspring of dams exposed to a mild ethanol...
Prenatal alcohol exposure (PAE) provokes lifelong CNS dysfunction, including an increased susceptibility to seizure disorders. We investigated hippocampal excitability in the offspring of dams exposed to a mild ethanol concentration throughout pregnancy (ethanol 15%v/v in drinking water). Hippocampal slices were prepared from the offspring at a young (Y, 21-30 postnatal days, PND) or adult (A, 60 PND) age, with controls from same age normal rats (N). Synchronous spontaneous interictal-type epileptiform discharges (IEDs) were induced by bathing the slices in Mg-free ACSF or in 4-Aminopyridine (4-AP, 50µΜ) and were recorded from CA1 pyramidal layer of temporal (T) and septal slices (S). Hippocampal slices readily generated IEDs following NMDA receptor activation or K conductance block, with frequency and duration depending on location (septal or temporal), age, the activating mechanism, and prior conditioning (N or PAE). From the two media, 4-AP induced higher frequency (always), shorter duration (mostly) IEDs compared to Mg -free ACSF. Temporal IED frequency increased with age, whereas septal was stable, indicating an earlier maturation of the latter part. The hippocampal "T to S" (high to low) excitability gradient appeared at/later than the end of the first postnatal month and mostly concerned discharge frequency. Discharge duration generally decreased with maturation but appeared to depend on many factors, including conditioning. Prenatal alcohol exposure differentiated the control of synchronous discharges by NMDA receptors and K conductances, and their developmental evolution, thus suggesting potential mechanisms for aberrant hippocampal neuronal network function.
Evidence of Swim secretion and association with extracellular matrix in the embryo.
Kaltezioti V, Vakaloglou KM, Charonis AS … +1 more , Zervas CG
Int J Dev Biol · 2022 · PMID 34881800 · Publisher ↗
Secreted wingless-interacting protein (Swim) is the ortholog gene of the mammalian Tubulointerstitial Nephritis Antigen like 1 (TINAGL1), also known as lipocalin-7 (LCN7), or adrenocortical zonation factor 1 (AZ-1). Swi...
Secreted wingless-interacting protein (Swim) is the ortholog gene of the mammalian Tubulointerstitial Nephritis Antigen like 1 (TINAGL1), also known as lipocalin-7 (LCN7), or adrenocortical zonation factor 1 (AZ-1). Swim and TINAGL1 proteins share a significant homology, including the somatomedin B and the predictive inactive C1 cysteine peptidase domains. In mammals, both TINAGL1 and its closely related homolog TINAG have been identified in basement membranes, where they may function as modulators of integrin-mediated adhesion. In , Swim was initially identified in the eggshell matrix and was subsequently detected in the culture medium of S2 cells. Further biochemical analysis indicated that Swim binds to wingless (wg) in a lipid-dependent manner. This observation, together with RNAi-knockdown studies, suggested that Swim is an essential cofactor of wg-signalling. However, recent elegant genetic studies ruled out the possibility that Swim is required alone to facilitate wg-signalling in , because flies without Swim are viable and fertile. Here, we use the UAS/Gal4 expression system together with confocal imaging to analyze the localization of a chimeric Swim-GFP in the developing embryo. Our data fully support the notion that Swim is an extracellular matrix component that is secreted upon ectopic expression and preferentially associates with the basement membranes of various organs and with the specialized tendon matrix at the muscle attachment sites (MAS). Interestingly, the accumulation of Swim at the MAS does not require integrins. In conclusion, Swim is an extracellular matrix component, and Swim may exhibit overlapping functions in concert with other undefined components.
Vascular cell-matrix adhesion in development and cancer.
Arapatzi C, Rouni G, Kostourou V
Int J Dev Biol · 2022 · PMID 34881799 · Publisher ↗
The development and homeostasis of vertebrate organisms depend on the "tree of life", in other words, the intricate network of vascular tubes composed of endothelial cells attached to the basement membrane and surrounded...
The development and homeostasis of vertebrate organisms depend on the "tree of life", in other words, the intricate network of vascular tubes composed of endothelial cells attached to the basement membrane and surrounded by perivascular cells. Although many studies have revealed the fundamental role of cytokines, growth factors and Notch signalling in vascular morphogenesis, we still lack sufficient understanding of the molecular mechanisms controlling the various steps of the angiogenic processes. Emerging data highlight that cell adhesions are key players in vascular morphogenesis. In this review, we focus on endothelial cells and we present the current state of knowledge regarding the role of cell-matrix adhesions in developmental and tumour angiogenesis, attained mainly from genetic studies and animal models.
Expression of marks a subset of enteroendocrine cells in the embryonic and larval midgut.
Skafida E, Delidakis C, Monastirioti M
Int J Dev Biol · 2022 · PMID 34881798 · Publisher ↗
Hey is a conserved transcription factor of the bHLH-Orange family that participates in the response to Notch signaling in certain tissues. Whereas three Hey paralogues exist in mammalian genomes, possesses a single gen...
Hey is a conserved transcription factor of the bHLH-Orange family that participates in the response to Notch signaling in certain tissues. Whereas three Hey paralogues exist in mammalian genomes, possesses a single gene. Fly Hey is expressed in the subset of newborn neurons that receive a Notch signal to differentiate them from their sibling cells after the asymmetric division of precursors called ganglion-mother-cells. We used a polyclonal anti-Hey serum and a GFP-tagged transgenic duplication of the locus to examine its expression in tissues outside the nervous system in embryos and larvae. We detected robust Hey expression in the embryonic midgut primordium at the time of birth of enteroendocrine cells, identified by expression of Prospero. Approximately half of the Pros-positive cells were also Hey positive at mid-embryogenesis. By the end of embryogenesis, most enteroendocrine cells had downregulated Hey expression, although it was still detectable at low levels after hatching. Low levels of Hey were also detected in subsets of the epithelial enterocytes at different times. Embryo enteroendocrine Hey expression was found to be Notch dependent. In late third-instar larvae, when few new enteroendocrine cells are born, novel Hey expression was detected in one cell of each sibling pair. In conclusion, Hey is strongly expressed in one of each pair of newly-born enteroendocrine cells. This is consistent with a hypothesis that embryonic enteroendocrine cells are born by an asymmetric division of a precursor, where Notch/Hey probably distinguish between the subtypes of these cells upon their differentiation.
Lipid rafts integrity is essential for prolactin-induced mitogenesis in mouse embryonic stem cells.
Karouzaki S, Peta C, Tsirimonaki E … +4 more , Leondaritis G, Vougas K, Tsangaris GT, Mangoura D
Int J Dev Biol · 2022 · PMID 34881797 · Publisher ↗
Embryonic stem cells, ESCs, retain the capacity to self-renew, yet, the protein machinery essential in maintaining this undifferentiated status remains largely undefined. Signalling interactions are initiated and enhance...
Embryonic stem cells, ESCs, retain the capacity to self-renew, yet, the protein machinery essential in maintaining this undifferentiated status remains largely undefined. Signalling interactions are initiated and enhanced at the plasma membrane lipid rafts, within constraints and regulations applied by the actin and tubulin cytoskeleton systems. First, we undertook a comprehensive approach using two-dimensional gel electrophoresis and mass spectrometry analysis combined with Western blotting and immunofluorescence analyses at the single cell level to compile the proteome profile of detergent-free preparations of lipid rafts of E14 mouse embryonic stem cells. In comparison with the proteomic profiles of other membrane fractions, recovery of actin and tubulin network proteins, including folding chaperones, was impressively high. At equally high frequency, we detected annexins, pleiotropic proteins that may bind membrane lipids and actin filaments to regulate important membrane processes, and we validated their expression in lipid rafts. Next, we tested whether lipid raft integrity is required for completion of mitogenic signalling pathways. Disruption of the rafts with the cholesterol sequestering methyl-β-cyclodextrin (MCD) greatly downregulated the mitotic index of ESCs, in a dose- and time of exposure-dependent manner. Moreover, MCD greatly reduced the mitogenic actions of prolactin, a hormone known to stimulate proliferation in a great variety of stem and progenitor cells. Taken together, our data postulate that lipid rafts in ESCs act in close association with the actin and tubulin cytoskeletons to support signal compartmentalization, especially for signalling pathways pertinent to symmetric divisions for self-renewal.
Age-dependent modulation of short-term neuronal dynamics in the dorsal and ventral rat hippocampus.
Trompoukis G, Tsotsokou G, Koutsoumpa A … +3 more , Tsolaki M, Vryoni G, Papatheodoropoulos C
Int J Dev Biol · 2022 · PMID 34881796 · Publisher ↗
Brain aging is associated with alterations in the behavioral capacity to process information, due to mechanisms that are still largely unclear. Short-term neuronal activity dynamics are basic properties of local brain ne...
Brain aging is associated with alterations in the behavioral capacity to process information, due to mechanisms that are still largely unclear. Short-term neuronal activity dynamics are basic properties of local brain networks profoundly involved in neural information processing. In this study, we investigated the properties of short-term changes in excitatory synaptic transmission and neuronal excitation in the CA1 field of dorsal and ventral hippocampal slices from young adult and old rats. We found that short-term synaptic plasticity (i.e. short-term dynamics of input to CA1 circuit) does not significantly differ between young and old dorsal or ventral hippocampus. However, short-term dynamics of hippocampal output differ markedly between young and old rats. Notably, age-dependent alterations in short-term neuronal dynamics were detected mainly in the dorsal hippocampus. Thus, the dorsal hippocampus of young rats can detect and facilitate transmission of 1-30 Hz input and depress transmission of higher-frequency input. In contrast, the old dorsal hippocampus appears unable to transmit information in a frequency-dependent discriminatory manner. Furthermore, the amplification of steady-state output at frequencies < 40 Hz is considerably lower in the old than the young dorsal hippocampus. The old ventral hippocampus did not show major alterations in short-term processing of neural information, though under conditions of intense afferent activation, neuronal output of the ventral hippocampus is depressed at steady-state more in old than in young rats. These results suggest that aging is accompanied by alterations in neural information processing mainly in the dorsal hippocampus, which displays a narrower dynamic range of frequency-dependent transient changes in neuronal activity in old compared with young adult rats. These alterations in short-term dynamics may relate to deficits in processing ongoing activity seen in old individuals.
RNA silencing pathways in plant development and defense.
Kryovrysanaki N, James A, Tselika M … +2 more , Bardani E, Kalantidis K
Int J Dev Biol · 2022 · PMID 34881795 · Publisher ↗
RNA silencing refers to a conserved eukaryotic process and is regarded as one of the most important processes in plants, with the ability to regulate gene expression both transcriptionally and post-transcriptionally. Dif...
RNA silencing refers to a conserved eukaryotic process and is regarded as one of the most important processes in plants, with the ability to regulate gene expression both transcriptionally and post-transcriptionally. Different classes of non-coding RNAs (ncRNAs) constitute key components of the RNA silencing pathways and play pivotal roles in modulating various biological processes as well as host-pathogen interactions. One of the most extensively studied classes of ncRNAs are the 20-24 nucleotide (nt) long microRNAs (miRNAs), which are core components of the endogenous gene silencing pathway. miRNAs act as negative regulators of endogenous gene expression through either mRNA-target cleavage, translational inhibition, or DNA methylation, and are inextricably linked to a plethora of developmental processes, such as leaf pattern formation as well as abiotic and biotic stress responses. In this review, we focus on the role of the RNA silencing pathways in the regulation of developmental processes as well as in the plant responses to biotic stress.
Repression of differentiation genes by Hes transcription factors fuels neural tumour growth in .
Voutyraki C, Choromidis A, Theodorou V … +6 more , Efraimoglou C, Anagnostopoulos G, Magadi SS, Grammenoudi S, Zacharioudaki E, Delidakis C
Int J Dev Biol · 2022 · PMID 34881794 · Publisher ↗
BACKGROUND: Neural stem cells (NSC) in divide asymmetrically to generate one cell that retains stem cell identity and another that is routed to differentiation. Prolonged mitotic activity of the NSCs gives rise to the pl...
BACKGROUND: Neural stem cells (NSC) in divide asymmetrically to generate one cell that retains stem cell identity and another that is routed to differentiation. Prolonged mitotic activity of the NSCs gives rise to the plethora of neurons and glial cells that wire the brain and nerve cord. Genetic insults, such as excess of Notch signaling, perturb the normal NSC proliferation programs and trigger the formation of NSC hyperplasias, which can subsequently progress to malignancies. Hes proteins are crucial mediators of Notch signaling, and in the NSC context they act by repressing a cohort of early pro-differentiation transcription factors. Downregulation of these pro-differentiation factors makes NSC progeny cells susceptible to adopting an aberrant stem cell program. We have recently shown that overexpression in leads to NSC hyperplasias that progress to malignant tumours after allografting to adult hosts. METHODS: We have combined genetic analysis, tissue allografting and transcriptomic approaches to address the role of genes in NSC malignant transformation. RESULTS: We show that the genes are important mediators in the progression of Notch hyperplasias to malignancy, since allografts lacking the genes grow much more slowly. We further present RNA profiling of -induced tumours at two different stages after allografting. We find that the same cohort of differentiation-promoting transcription factors that are repressed in the primary hyperplasias continue to be downregulated after transplantation. This is accompanied by an upregulation of stress-response genes and metabolic reprogramming. CONCLUSIONS: The combination of dedifferentiation and cell physiology changes most likely drive tumour growth.
Cortical interneuron development: a role for small Rho GTPases.
Kounoupa Z, Karagogeos D
Int J Dev Biol · 2022 · PMID 34881793 · Publisher ↗
GABAergic interneurons control cortical excitation/inhibition balance and are implicated in severe neurodevelopmental disorders. In contrast to the multiplicity of signals underlying the generation and migration of corti...
GABAergic interneurons control cortical excitation/inhibition balance and are implicated in severe neurodevelopmental disorders. In contrast to the multiplicity of signals underlying the generation and migration of cortical interneurons, the intracellular proteins mediating the response to these cues are largely unknown. We have demonstrated the unique and diverse roles of the Rho GTPases Rac1 and 3 in cell cycle and morphology in transgenic animals where Rac1 and Rac1/3 were ablated specifically in cortical interneurons. In the Rac1 mutant, progenitors delay their cell cycle exit, probably due to a prolonged G1 phase resulting in a cortex with 50% reductions in interneurons and an imbalance of excitation/inhibition in cortical circuits. This disruption in GABAergic inhibition alters glutamatergic function in the adult cortex, which could be reversed by enhancement of GABAergic functions during an early postnatal period. Furthermore, this disruption disturbs neuronal synchronization in the adult cortex. In the double mutant, additional severe cytoskeletal defects result in an 80% interneuron decrease. Both lines die postnatally from epileptic seizures. We have made progress towards characterizing the cell cycle defect in Rac1 mutant interneuron progenitors, determining the morphological and synaptic characteristics of single and double mutant interneurons and identifying some of the molecular players through which Racs exert their actions via proteomic analysis. In our present work, we review these studies and discuss open questions and future perspectives. We hope that our data will contribute to the understanding of the function of cortical interneurons, especially since preclinical models of interneuron-based cell therapies are being established.
The development of MGE-derived cortical interneurons: An Lhx6 tale.
Christodoulou O, Maragkos I, Antonakou V … +1 more , Denaxa M
Int J Dev Biol · 2022 · PMID 34881792 · Publisher ↗
The cerebral cortex contains two main neuronal cell populations: the excitatory pyramidal neurons and the inhibitory interneurons, which constitute 20-30% of all cortical neurons. Cortical interneurons are characterized...
The cerebral cortex contains two main neuronal cell populations: the excitatory pyramidal neurons and the inhibitory interneurons, which constitute 20-30% of all cortical neurons. Cortical interneurons are characterized by a remarkable morphological, molecular and functional diversity. A swathe of research activity over the last 20 years has sought to determine how cortical interneurons acquire their mature cellular and functional features, and has identified a number of transcription factors that function at different stages of interneuron development. Here, we review all current knowledge concerning the multiple functions of the "master regulator" - LIM-Homeodomain transcription factor Lhx6 - a gene expressed in the medial ganglionic eminence of the basal telencephalon that controls the development of somatostatin and parvalbumin expressing interneurons.
Epithelial-to-mesenchymal transition of tumor cells: cancer progression and metastasis.
Vardas V, Politaki E, Pantazaka E … +2 more , Georgoulias V, Kallergi G
Int J Dev Biol · 2022 · PMID 34881791 · Publisher ↗
Detection and characterization of circulating tumor cells (CTCs) with an epithelial-to-mesenchymal transition (EMT) phenotype is very important, as it can contribute to the identification of high-risk for relapse and dea...
Detection and characterization of circulating tumor cells (CTCs) with an epithelial-to-mesenchymal transition (EMT) phenotype is very important, as it can contribute to the identification of high-risk for relapse and death patients. However, most methods underestimate CTC numbers, owing to their dependence on epithelial markers. In the current study, we evaluated the EMT phenotype in CTCs isolated from breast cancer (BC) patients, using the CellSearch system. Spiking experiments for the evaluation of the specificity and sensitivity of our method were performed using HeLa cells. Sixty-five breast cancer (BC) patients (47 early and 18 metastatic) were enrolled in the study. Vimentin is a mesenchymal marker that indicates tumoral cells acquiring invasive and malignant properties. We studied vimentin (VIM) expression using the extra channel of the CellSearch system and an anti-vimentin antibody conjugated with FITC. In our present results, we reported the percentage of circulating tumor cells that expressed vimentin in early and in metastatic breast cancer patients. Interestingly, the incidence of cells with a CK-VIM+CD45- phenotype was detected in both settings. These cells were detected in 31.4% of CK-negative (11/35) and 82.3% of CK-positive (10/12) early BC patients. The corresponding numbers for metastatic disease were 15.4% (2/13) and 100% (5/5), respectively. Our results suggest that in CTC-negative patients, potentially undetectable tumor cells could be identified using the FDA-approved CellSearch system, based on the (CK-VIM+CD45-)-phenotype, offering additional information regarding metastatic dissemination in cancer patients. Further experiments evaluating more biomarkers are necessary to elucidate the mechanisms that regulate tumorigenesis and metastasis.
Vascular Endothelial (VE)-cadherin-mediated adherens junctions involvement in cardiovascular progenitor cell specification.
Maltabe V, Kouklis P
Int J Dev Biol · 2022 · PMID 34881790 · Publisher ↗
Vascular Endothelial cadherin, a type II classical cadherin, is the major cadherin molecule participating in homotypic cell-cell adhesion structures between endothelial cells. It associates with cytoplasmic and membrane...
Vascular Endothelial cadherin, a type II classical cadherin, is the major cadherin molecule participating in homotypic cell-cell adhesion structures between endothelial cells. It associates with cytoplasmic and membrane cytoskeletal elements to form endothelial adherens junctions (AJs), pivotal in regulating endothelial barrier function in the adult. VE-cadherin-mediated AJs are also involved in signaling via direct or indirect associations with receptors. The generation of mutant animals, especially mice and zebrafish, revealed many details concerning the role of VE-cadherin-mediated AJs in cardiovascular development. In general, knockout (KO) in mice is embryonic lethal due to severe cardiovascular defects, and major signaling pathways as well as vascular formation cues were discovered in developing endothelium. However, there is little information regarding AJs formation and their components in cardiovascular progenitors. We have characterized in detail the activation pattern of mouse promoter (Pvec) in a mouse embryonic stem cells (ESCs) differentiation system Surprisingly, we found that it is activated transiently in cardiac progenitors that belong to the second heart field. Based on Pvec activation, we isolated this population and found that it can self-renew by induction of the Wnt/β-catenin pathway. Next, we successfully established cell culture conditions that allowed self-renewal of this population that consists of endothelial and cardiac progenitors. Transplantation in rat hearts showed that they can survive and differentiate to cardiomyocytes and endothelial cells. Although further characterization is needed, these cells can be used in cell-based therapies as well as in drug screening.
Expression of D5 dopamine receptors in the lateral ventricle walls during post-weaning rat development.
Prosilis A, Mesiakaris V, Stamatakis A
Int J Dev Biol · 2022 · PMID 34881789 · Publisher ↗
Even before the first synapses appear, neurotransmitters and their receptors are present in the developing brain, regulating the cell fate of neuronal progenitors in neurogenic niches, such as the lateral ventricle. In p...
Even before the first synapses appear, neurotransmitters and their receptors are present in the developing brain, regulating the cell fate of neuronal progenitors in neurogenic niches, such as the lateral ventricle. In particular, dopamine appears to play a pivotal role in the neurogenesis of the subventricular zone by controlling the proliferation and differentiation of progenitors through activation of different receptors. Although dopamine receptor 5 (D5R) is expressed prenatally, there is little information regarding its role in either pre- or postnatal forebrain development. To examine the role of D5Rs in neurogenesis in the rat lateral ventricle subventricular zone (V-SVZ), we immunohistochemically defined D5R expression, as well as BrdU incorporation in progenitor cells of various post-weaning stages (Post-natal day (P) 20 until P80). We found that the level of proliferating cells is stable from postnatal day 20 until 50, and then declines sharply on P80. Concomitantly, D5R is expressed in all ages examined, but we detected a progressive decrease in the density of D5R+ cells from P40 until P80. Moreover, double immunostaining for BrdU and D5R revealed that proliferating cells in V-SVZ also express D5R. Collectively, our data suggest that D5R is expressed in the post-weaning V-SVZ of rat at least until P80, and its expression pattern coincides with that of proliferating cells in the V-SVZ, hinting at a possible role of D5Rs in the regulation of neuronal progenitor division/differentiation.
Keratinocyte differentiation and proteolytic pathways in skin (patho) physiology.
Zingkou E, Pampalakis G, Sotiropoulou G
Int J Dev Biol · 2022 · PMID 34881788 · Publisher ↗
The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of differentiation. The stratum corneum is the outermost...
The epidermis is a stratified epithelium that forms the barrier between the organism and its environment. It is mainly composed of keratinocytes at various stages of differentiation. The stratum corneum is the outermost layer of the epidermis and is formed of multiple layers of anucleated keratinocytes called corneocytes. We aim to highlight the roles of epidermal differentiation and proteolysis in skin diseases. Skin biopsies isolated from mice, the established model of Netherton syndrome (NS), and from patients with NS, seborrheic dermatitis (SD) and psoriasis, as well as healthy controls, were analyzed by histology and immunohistochemistry. Our results showed that NS, SD, and psoriasis are all characterized by abnormal epidermal differentiation, manifested by hyperplasia, hyperkeratosis, and parakeratosis. At the molecular level, abnormal differentiation is accompanied by increased expression of involucrin and decreased expression of loricrin in NS and psoriasis. Increased epidermal proteolysis associated with increased kallikrein-related peptidases (KLKs) expression is also observed in both NS and psoriatic epidermis. Furthermore, reduced expression of desmosomal proteins is observed in NS, but increased in psoriasis. Since desmosomal proteins are proteolytic substrates and control keratinocyte differentiation, their altered expression directly links epidermal proteolysis to differentiation. In conclusion, abnormal cellular differentiation and proteolysis are interconnected and underlie the pathology of NS, SD and psoriasis.
Developmental and regenerative biology of cardiomyocytes.
Daiou A, Petalidou K, Siokatas G … +2 more , Papadopoulos EI, Hatzistergos KE
Int J Dev Biol · 2022 · PMID 34881787 · Publisher ↗
Current progress and challenges in understanding the molecular and cellular mechanisms of cardiomyocyte embryonic development and regeneration are reviewed in our present work. Three major topics are critically discussed...
Current progress and challenges in understanding the molecular and cellular mechanisms of cardiomyocyte embryonic development and regeneration are reviewed in our present work. Three major topics are critically discussed: how do cardiomyocytes form in the embryo? What is the adult origin of the cells that regenerate cardiomyocytes in animal models with adult heart regeneration capabilities? Can the promise of therapeutic cardiomyocyte regeneration be realized in humans? In the first topic, we highlight current advances in understanding the developmental biology of cardiomyocytes, with emphasis on the regulative capabilities of the early embryo during specification and allocation of the cardiomyoblasts that produce the primordial heart. We place further emphasis on trabecular cardiomyocyte development from late cardiomyoblasts, neural crest cells and primordial cardiomyocytes, and their critical role in the clonal growth of the compact/septal and cortical cardiomyocyte layers in the mammalian embryo and adult zebrafish, respectively. In the second topic, we focus on the re-activation of the cortical or trabecular compaction programs as hallmarks of cardiomyocyte regenerative cells during adult zebrafish and neonatal mouse heart regeneration, respectively, and underscore the metabolic remodeling that commonly drives cardiomyocyte regeneration in these organisms. Finally, we discuss the status of preclinical and clinical-stage therapeutics for cardiomyocyte regeneration, with particular emphasis on gene therapy, as well as adult and pluripotent stem cell-based cellular cardiomyoplasty approaches. In summary, our article provides a bird's-eye view of current knowledge and potential pitfalls in the field of developmental biology-guided regenerative medicine strategies for the treatment of heart diseases.
Organoids: the third dimension of human brain development and disease.
Kouroupi G, Prodromidou K, Papastefanaki F … +2 more , Taoufik E, Matsas R
Int J Dev Biol · 2022 · PMID 34881786 · Publisher ↗
Stem cell technologies have opened up new avenues in the study of human biology and disease. In particular, the advent of human embryonic stem cells followed by reprograming technologies for generation of induced pluripo...
Stem cell technologies have opened up new avenues in the study of human biology and disease. In particular, the advent of human embryonic stem cells followed by reprograming technologies for generation of induced pluripotent stem cells have instigated studies into modeling human brain development and disease by providing a means to simulate a human tissue otherwise completely or largely inaccessible to researchers. Brain development is a complex process achieved in a remarkably controlled spatial and temporal manner through coordinated cellular and molecular events. models aim to mimic these processes and recapitulate brain organogenesis. Initially, two-dimensional neural cultures presented an innovative landmark for investigating human neuronal and, more recently, glial biology, as well as for modeling brain neurodevelopmental and neurodegenerative diseases. The establishment of three-dimensional cultures in the form of brain organoids was an equally important milestone in the field. Brain organoids mimic more closely the tissue composition and architecture and are more physiologically relevant than monolayer cultures. They therefore represent a more realistic cellular environment for modeling the cell biology and pathology of the nervous system. Here we highlight the journey towards recapitulating human brain development and disease in a dish, progressing from two-dimensional systems to the third dimension provided by brain organoids. We discuss the potential of these approaches for modeling human brain development and evolution, and their promising contribution towards understanding and treating brain disease.
Promyelocytic leukemia protein (PML) and stem cells: from cancer to pluripotency.
Vogiatzoglou AP, Moretto F, Makkou M … +2 more , Papamatheakis J, Kretsovali A
Int J Dev Biol · 2022 · PMID 34881785 · Publisher ↗
The promyelocytic leukemia protein (PML) is the core organizer of cognate nuclear bodies (PML-NBs). Through physical interaction or modification of diverse protein clients, PML-NBs regulate a multitude of - often antithe...
The promyelocytic leukemia protein (PML) is the core organizer of cognate nuclear bodies (PML-NBs). Through physical interaction or modification of diverse protein clients, PML-NBs regulate a multitude of - often antithetical- biological processes such as antiviral and stress response, inhibition of cell proliferation and autophagy, and promotion of apoptosis or senescence. Although PML was originally recognized as a tumor-suppressive factor, more recent studies have revealed a "double-faced" agent role for PML. Indeed, PML displayed tumor cell pro-survival and pro-migratory functions via inhibition of migration suppressing molecules or promotion of transforming growth factor beta (TGF-β) mediated Epithelial-Mesenchymal Transition (EMT) that may promote cancer cell dissemination. In this line, PML was found to correlate with poor patient prognosis in distinct tumor contexts. Furthermore, in the last decade, a number of publications have implicated PML in the physiology of normal or cancer stem cells (CSCs). Promyelocytic leukemia protein activates fatty acid oxidation (FAO), a metabolic mechanism required for the asymmetric divisions and maintenance of hematopoietic stem cells (HSCs). In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), PML is required for maintenance of the naïve and acquisition of the induced pluripotency state, respectively. Correspondingly, PML ablation causes significant morphological gene expression and lineage choice changes. In this review, we focus on the mechanisms orchestrated by PML and PML-NBs in cancer and healthy stem cells, from cell physiology to the regulation of chromatin dynamics.
Spatial distribution of blood vessels in the chick embryo chorioallantoic membrane.
Guidolin D, Tamma R, Annese T … +2 more , Tortorella C, Ribatti D
Int J Dev Biol · 2021 · PMID 34881784 · Publisher ↗
The chick embryo chorioallantoic membrane (CAM) is a useful tool with which to study both angiogenesis and anti-angiogenesis in vivo. CAM vascular growth pattern - including the way through vessels fills the available sp...
The chick embryo chorioallantoic membrane (CAM) is a useful tool with which to study both angiogenesis and anti-angiogenesis in vivo. CAM vascular growth pattern - including the way through vessels fills the available space - can be quite easily described and quantified using image analysis procedures, in order to evaluate different parameters, including fractal dimension, lacunarity and non-fractal order-disorder parameters. In the present study, we further expanded this morphological description, by estimating an index expressing the degree of symmetry characterizing the CAM vascular tree structure in the course of the embryonic development. Moreover, a uniformity index was estimated quantitatively to characterize the space-filling features of the vessels, i.e. the degree of spatial uniformity of their distribution in the tissue.
Molecular characterization of the prostaglandin E receptor subtypes 2a and 4b and their expression patterns during embryogenesis in zebrafish.
Han Y, Chang H, Wu H
Int J Dev Biol · 2021 · PMID 34549801 · Publisher ↗
The molecular expression profiles of zebrafish and have not been defined to date. Phylogenetic trees of EP2a and EP4b in zebrafish and other species revealed that human EP4 and zebrafish EP4b were more closely related...
The molecular expression profiles of zebrafish and have not been defined to date. Phylogenetic trees of EP2a and EP4b in zebrafish and other species revealed that human EP4 and zebrafish EP4b were more closely related than EP2a. Zebrafish EP2a is a 281 amino acid protein which shares high identity with that of human (43%), mouse (44%), rat (43%), dog (44%), cattle (41%), and chicken (41%). Zebrafish EP4b encoded a 497 amino acid precursor with high amino acid identity to that of mammals, including human (57%), mouse (54%), rat (55%), dog (55%), cattle (56%), and chicken (54%). Whole-mount hybridization revealed that was robustly expressed in the anterior four somites at the 10-somites stages, but was absent in the somites at 19 hpf. It was observed again in the pronephric duct at 24 hpf, in the intermediate cell mass located in the trunk, and in the rostral blood island at 30 hpf. was also expressed in the notochord at 48 hpf. During somitogenesis, was highly expressed in the eyes, somites, and the trunk neural crest. From 30 to 48 hpf, could be detected in the posterior cardinal vein and the neighboring inner cell mass. From these data we conclude that and are conserved in vertebrates and that the presence of and transcripts during developmental stages infers their role during early zebrafish larval development. In addition, the variable expression of the two receptor isoforms was strongly suggestive of divergent roles of molecular regulation.
Mitotic timing is differentially controlled by A- and B-type cyclins and by CDC6 associated with a CDK inhibitor Xic1 in cell-free extract.
El Dika M, Wechselberger L, Djeghout B … +7 more , Benouareth DE, Jęderka K, Lewicki S, Zdanowski R, Prigent C, Kloc M, Kubiak JZ
Int J Dev Biol · 2021 · PMID 34549800 · Publisher ↗
The timing of the M-phase is precisely controlled by a CDC6-dependent mechanism inhibiting the mitotic histone H1 kinase. Here, we describe the differential regulation of the dynamics of this mitotic kinase activity by e...
The timing of the M-phase is precisely controlled by a CDC6-dependent mechanism inhibiting the mitotic histone H1 kinase. Here, we describe the differential regulation of the dynamics of this mitotic kinase activity by exogenous cyclin A or cyclin B in the cycling extracts. We show that the experimental increase in cyclin A modifies only the level of histone H1 kinase activity, while the cyclin B increase modifies two parameters: histone H1 kinase activity and the timing of its full activation, which is accelerated. On the other hand, the cyclin A depletion significantly delays full activation of histone H1 kinase. However, when CDC6 is added to such an extract, it inhibits cyclin B-associated histone H1 kinase, but does not modify the mitotic timing in the absence of cyclin A. Further, we show via p9 co-precipitation with Cyclin-Dependent Kinases (CDKs), that both CDC6 and the CDK1 inhibitor Xic1 associate with the mitotic CDKs. Finally, we show that the Xic1 temporarily separates from the mitotic CDKs complexes during the peak of histone H1 kinase activity. These data show the differential coordination of the M-phase progression by cyclin A- and cyclin B-dependent CDKs, confirm the critical role of the CDC6-dependent histone H1 kinase inhibition in this process, and show that CDC6 acts differentially through the cyclin B- and cyclin A-associated CDKs. This CDC6- and cyclins-dependent mechanism likely depends on the precisely regulated association of Xic1 with the mitotic CDKs complexes. We postulate that: i. the dissociation of Xic1 from the CDKs complexes allows the maximal activation of CDK1 during the M-phase, ii. the switch between cyclin A- and cyclin B-CDK inhibition upon M-phase initiation may be responsible for the diauxic growth of mitotic histone H1 kinase activity.
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