Differentiation; Research in Biological Diversity

Adult male Sertoli cell-specific Connexin43 knockout mice (SCCx43KO) exhibit higher Sertoli cell (SC) numbers per seminiferous tubule compared to their wild type (WT) littermates. Thus, deletion of this testicular gap junction protein seems to affect the proliferative potential and differentiation of "younger" SC. Although SC have so far mostly been characterised as postmitotic cells that cease to divide and become an adult, terminally differentiated cell population at around puberty, there is rising evidence that there exist exceptions from this for a very long time accepted paradigm...

The vascular system plays a crucial role in bone tissue. Angiogenic and osteogenic processes are coupled through a spatial-temporal connection. Recent studies have identified three types of capillaries in the skeletal system. Compared with type L and E vessels, type H vessels express high levels of CD31 and endomucin, and function to couple angiogenesis and osteogenesis. Endothelial cells in type H vessels interact with osteolineage cells (e.g., osteoblasts, osteoclasts, and osteocytes) through cytokines or signaling pathways to maintain bone growth and homeostasis...

Fibroblast growth factor 9 (FGF9) was first identified during a screen for factors acting on cells of the central nervous system (CNS). Research over the subsequent two decades has revealed this protein to be a critically important and elegantly regulated growth factor. A hallmark control feature is reciprocal compartmentalization, particularly during development, with epithelium as a dominant source and mesenchyme a prime target. This mesenchyme selectivity is accomplished by the high affinity of FGF9 to the IIIc isoforms of FGFR1, 2, and 3...

Though initially discovered as a proto-oncogene in virally induced mouse mammary tumors, FGF3 is primarily active in prenatal stages, where it is found at various sites at specific times. FGF3 is crucial during development, as its roles include tail formation, inner ear development and hindbrain induction and patterning. FGF3 expression and function are highly conserved in vertebrates, while it also interacts with other FGFs in various developmental processes. Intriguingly, while it is classified as a classical paracrine signaling factor, murine FGF3 was uniquely found to also act in an intracrine manner, depending on alternative translation initiation sites...

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial disease that is characterized by increased cellular proliferation and differentiation together with excessive extracellular matrix (ECM) deposition leading to buildup of scar tissue (fibrosis) and remodeling in the lungs. The activated and differentiated (myo)fibroblasts are one of the main sources of tissue remodeling in IPF and a crucial mechanism known to contribute to this feature is an aberrant crosstalk between pulmonary fibroblasts and the abnormal or injured pulmonary epithelium...

Barrett's oesophagus (BO) is a pathological condition in which the squamous epithelium of the distal oesophagus is replaced by an intestinal-like columnar epithelium originating from the gastric cardia. Several somatic mutations contribute to the intestinal-like metaplasia. Once these have occurred in a single cell, it will be unable to expand further unless the altered cell can colonise the surrounding squamous epithelium of the oesophagus. The mechanisms by which this happens are still unknown. Here we have established an in vitro system for examining the competitive behaviour of two epithelia...

Diabetes mellitus (DM) and osteoporosis are two major health care problems worldwide. Emerging evidence suggests that DM poses a risk for osteoporosis and can contribute to the development of diabetes-induced osteoporosis (DOP). Interestingly, some epidemiological studies suggest that DOP may be at least partially distinct from those skeletal abnormalities associated with old age or postmenopausal osteoporosis. The increasing number of DM patients who also have DOP calls for a discussion of the pathogenesis of DOP and the investigation of drugs to treat DOP...

This study investigated the expression of sortilin 1 (SORT1) in cultured human dental pulp-derived stem cells (hDPSCs) and its role in their odontoblastic differentiation. Permanent teeth were extracted from five patients, and the dental pulp was harvested for explant culture. Fluorescence-activated cell sorting was used to analyze the outgrowth of adherent cells and cells that had migrated from the tissue margin. SORT1 expression was detected in hDPSCs simultaneously expressing the mesenchymal stem cell markers CD44 and CD90...

Cartilage development is a tightly regulated process that requires the interaction of epithelial and mesenchymal tissues layers to initiate the aggregation of mesenchyme in a condensation. Several signaling molecules have been implicated in cartilage formation including FGFs, WNTs, and members of the TGF-β super family. However, little is known about the earliest signals involved in these initial phases of development. Here we aimed to investigate whether direct intravitreal injection of pharmaceutical inhibitors for FGF and TGF-β signaling would perturb cranial cartilages in zebrafish...

Precise spatiotemporal control of gene expression patterns is critical for normal development. Pluripotent stem cells, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with the ability of unlimited self-renewal and differentiation into any cell type, provide a unique tool for understanding the underlying mechanism of development and disease in a dish. N6-methyl-adenosine (m6 A) modification is the most extensive internal mRNA modification, which regulates almost all aspects of mRNA metabolism and thus extensively participates in gene expression regulation...

Mutations in SHH and several other genes encoding components of the Hedgehog signaling pathway have been associated with holoprosencephaly syndromes, with craniofacial anomalies ranging in severity from cyclopia to facial cleft to midfacial and mandibular hypoplasia. Studies in animal models have revealed that SHH signaling plays crucial roles at multiple stages of craniofacial morphogenesis, from cranial neural crest cell survival to growth and patterning of the facial primordia to organogenesis of the palate, mandible, tongue, tooth, and taste bud formation and homeostasis...

Cerebral palsy (CP) is one of the most common conditions leading to lifelong childhood physical disability. Literature reported previously altered muscle properties such as lower number of satellite cells (SCs), with altered fusion capacity. However, these observations highly vary among studies, possibly due to heterogeneity in patient population, lack of appropriate control data, methodology and different assessed muscle. In this study we aimed to strengthen previous observations and to understand the heterogeneity of CP muscle pathology...

The neural crest is a stem cell population that forms in the neurectoderm of all vertebrates and gives rise to a diverse set of cells such as sensory neurons, Schwann cells and melanocytes. Neural crest development in snakes is still poorly understood. From the point of view of evolutionary and comparative anatomy is an interesting topic given the unique anatomy of snakes. The aim of the study was to characterize how trunk neural crest cells (TNCC) migrate in the developing elapid snake Naja haje haje and consequently, look at the beginnings of development of neural crest derived sensory ganglia (DRG) and spinal nerves...

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The Drosophila melanogaster eye has been instrumental for determining both how cells communicate with one another to determine cell fate, as well as cell morphogenesis and patterning. Here, we describe the effects of the small GTPase Rap1 on the development of multiple cell types in the D. melanogaster eye. Although Rap1 has previously been linked to RTK-Ras-MAPK signaling in eye development, we demonstrate that manipulation of Rap1 activity is modified by increase or decrease of Delta/Notch signaling during several events of cell fate specification in eye development...

Palate development involves various events, including proliferation, osteogenic differentiation, and epithelial-mesenchymal transition. Disruption of these processes can result in the cleft palate (CP). Mouse embryonic palatal mesenchyme (MEPM) cells are commonly used to explore the mechanism of palatal development and CP. However, the role of the microenvironment in the biological properties of MEPM cells, which undergoes dynamic changes during palate development, is rarely reported. In this study, we investigated whether there were differences between the palatal shelf mesenchyme at different developmental stages...

The development of the hyoid bone is a complex process that involves the coordination of multiple signaling pathways. Previous studies have demonstrated that disruption of the hedgehog pathway in mice results in a series of structural malformations. However, the specific role and critical period of the hedgehog pathway in the early development of the hyoid bone have not been thoroughly characterized. In this study, we treated pregnant ICR mice with the hedgehog pathway inhibitor vismodegib by oral gavage in order to establish a model of hyoid bone dysplasia...

The Meibomian gland (MG) is an indispensable adnexal structure of eye that produces meibum, an important defensive component for maintaining ocular homeostasis. Normal development and maintenance of the MGs is required for ocular health since atrophic MGs and disturbances in composition and/or secretion of meibum result in major ocular pathologies, collectively termed as Meibomian gland dysfunction (MGD). Currently available therapies for MGD merely provide symptomatic relief and do not treat the underlying deficiency of the MGs...

Variants in the MMACHC gene cause combined methylmalonic acidemia and homocystinuria cblC type, the most common inborn error of intracellular cobalamin (vitamin B12) metabolism. cblC is associated with neurodevelopmental, hematological, ocular, and biochemical abnormalities. In a subset of patients, mild craniofacial dysmorphia has also been described. Mouse models of Mmachc deletion are embryonic lethal but cause severe craniofacial phenotypes such as facial clefts. MMACHC encodes an enzyme required for cobalamin processing and variants in this gene result in the accumulation of two metabolites: methylmalonic acid (MMA) and homocysteine (HC)...

SF3B proteins form a heptameric complex in the U2 small nuclear ribonucleoprotein, essential for pre-mRNA splicing. Heterozygous pathogenic variants in human SF3B4 are associated with head, face, limb, and vertebrae defects. Using the CRISPR/Cas9 system, we generated mice with constitutive heterozygous deletion of Sf3b4 and showed that mutant embryos have abnormal vertebral development. Vertebrae abnormalities were accompanied by changes in levels and expression pattern of Hox genes in the somites. RNA sequencing analysis of whole embryos and somites of Sf3b4 mutant and control litter mates revealed increased expression of other Sf3b4 genes...