Sclerotome

Adolescent idiopathic scoliosis (AIS), a sideways curvature of the spine, is sexually dimorphic, with increased incidence in females. A genome-wide association study identified a female-specific AIS susceptibility locus near the PAX1 gene. Here, we use mouse enhancer assays, three mouse enhancer knockouts, and subsequent phenotypic analyses to characterize this region. Using mouse enhancer assays, we characterize a sequence, PEC7, which overlaps the AIS-associated variant, and find it to be active in the tail tip and intervertebral disc...

Interactions between notochord and sclerotome are required for normal embryonic spine patterning, but whether the postnatal derivatives of these tissues also require interactions for postnatal intervertebral disc (IVD) growth and maintenance is less established. We report here the comparative analysis of four conditional knockout mice deficient for TonEBP/Nfat5, a transcription factor known to allow cells to adapt to changes in extracellular osmotic pressure, in specific compartments of the IVD. We show that TonEBP deletion in nucleus pulposus (NP) cells does not affect their survival or aggrecan expression, but promoted cell proliferation in the NP and in adjacent vertebral growth plates (GP)...

Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that some hematopoiesis-supporting cells originate from vSMC precursors. These pericyte-like precursors were recently identified in the aorta-gonad-mesonephros (AGM) region; however, their role in the hematopoietic development in vivo remains unknown. Here, we identify a subpopulation of NG2+ Runx1+ perivascular cells that display a sclerotome-derived vSMC transcriptomic profile...

INTRODUCTION: Therapeutic interventions for intervertebral disc herniation remain scarce due to the inability of endogenous annulus fibrosus (AF) cells to respond to injury and drive tissue regeneration. Unlike other orthopedic tissues, such as cartilage, delivery of exogenous cells to the site of annular injury remains underdeveloped, largely due to a lack of an ideal cell source and the invasive nature of cell isolation. Human induced pluripotent stem cells (iPSCs) can be differentiated to specific cell fates using biochemical factors and are, therefore, an invaluable tool for cell therapy approaches...

Skeletal tissues including cartilage and bones are characteristic features of vertebrates that are crucial for supporting body morphology and locomotion. Studies mainly in mice have shown that osteoblasts and chondroblasts are supplied from several progenitors like the sclerotome cells in the embryonic stage, osteo-chondroprogenitors in growing long bones, and skeletal stem cells of bone marrow in the postnatal period. However, the exact origins of progenitor cells, their lineage relationships, and their potential to differentiate into osteoblasts and chondroblasts from embryos to adult tissues are not well understood...

In anurans, the vertebral column diverges widely from that of other tetrapods; yet the molecular mechanisms underlying its morphogenesis remain largely unexplored. In this study, we investigate the role of the homeologous uncx.L and uncx.S genes in the vertebral column morphogenesis of the allotetraploid frog Xenopus laevis. We initiated our study by cloning the uncx orthologous genes in the anuran Xenopus and determining their spatial expression patterns using in situ hybridization. Additionally, we employed gain-of-function and loss-of-function approaches through dexamethasone-inducible uncx constructs and antisense morpholino oligonucleotides, respectively...

Atlanto-occipital assimilation is an osseous embryological anomaly of the craniovertebral junction in which the atlas (C1) is fused to the occiput of skull. Embryologically, this assimilation may happen due to failure of the segmentation and separation of the caudal occipital and the cranial cervical sclerotome. The segmentation clock is maintained by NOTCH and WNT signalling pathways along with Hox genes and retinoic acid. This condition is likely to be a consequence of mutation in above mentioned genes. The knowledge of this assimilation may be crucial for the clinicians as it may lead to various neurovascular symptoms...

BACKGROUND: Mural cells are an essential perivascular cell population that associate with blood vessels and contribute to vascular stabilization and tone. In the embryonic zebrafish vasculature, pdgfrb and tagln are commonly used as markers for identifying pericytes and vascular smooth muscle cells. However, the overlapping and distinct expression patterns of these markers in tandem have not been fully described. RESULTS: Here, we used the Tg(pdgfrb:Gal4FF; UAS:RFP) and Tg(tagln:NLS-EGFP) transgenic lines to identify single- and double-positive perivascular cell populations on the cranial, axial, and intersegmental vessels between 1 and 5 days postfertilization...

The somites are embryonic structures that give rise to the axial musculoskeletal system. In amniotes vertebrates, somites are composed of multipotent somitic cells that quickly compartmentalize into a dorsal dermomyotome and a ventral sclerotome. In the somites, the dermomyotome gives rise to skeletal muscle cells (the myotome) and the dorsal dermis (the dermatome), while the sclerotome gives rise to vertebrae, ribs, and dorsal tendons (the syndetome). The compartmentalization pattern differs in anamniotes, with the establishment of a primitive myotome that begins before somite formation while the LSF (lateral somitic frontier) give rise to both the sclerotome and the dermomyotome in Xenopus...

Serial block-face scanning electron microscopy of the tail tip of post-metamorphic amphioxus (Branchiostoma floridae) revealed some terminal myomeres never been seen before with other techniques. The morphology of these myomeres differed markedly from the chevron shapes of their more anterior counterparts. Histologically, these odd-shaped myomeres ranged from empty vesicles bordered by undifferentiated cells to ventral sacs composed of well-developed myotome, dermatome, and sclerotome. Strikingly, several of these ventral sacs gave rise to a nipple-like dorsal projection composed either entirely of sclerotome or a mixture of sclerotome and myotome...

In embryonic development, the vertebral column arises from the sclerotomal compartment of the somites. The sclerotome is a mesenchymal cell mass which can be subdivided into several subpopulations specified by different regulatory mechanisms and giving rise to different parts of the vertebrae like vertebral body, vertebral arch, ribs, and vertebral joints. This review gives a short overview on the molecular and cellular basis of the formation of sclerotomal subdomains and the morphogenesis of their vertebral derivatives...

Ciliopathies are associated with wide spectrum of structural birth defects (SBDs), indicating important roles for cilia in development. Here, we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140, an intraflagellar transport (IFT) protein regulating ciliogenesis. Ift140-deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula (TEF), randomized heart looping, congenital heart defects (CHDs), lung hypoplasia, renal anomalies, and polydactyly...

Despite their importance in tissue maintenance and repair, fibroblast diversity and plasticity remain poorly understood. Using single-cell RNA sequencing, we uncover distinct sclerotome-derived fibroblast populations in zebrafish, including progenitor-like perivascular/interstitial fibroblasts, and specialized fibroblasts such as tenocytes. To determine fibroblast plasticity in vivo, we develop a laser-induced tendon ablation and regeneration model. Lineage tracing reveals that laser-ablated tenocytes are quickly regenerated by preexisting fibroblasts...

Primitive erythropoiesis serves a vital role in embryonic development, generating primitive red blood cells responsible for transportation of oxygen throughout the body. Although diverse niche factors are known to function in definitive hematopoiesis, the microenvironment contributing to primitive hematopoiesis remains largely elusive. Here, we report that platelet-derived growth factor (PDGF) signaling is required for erythroid progenitor differentiation. Ablating pdgfαa and pdgfαb or blocking PDGF signaling with an inhibitor impairs erythroid progenitor differentiation, thus resulting in a significant decrease in the number of erythrocytes...

BACKGROUND: Although vertebrae are the defining character of vertebrates, they are found only in rudimentary form in extant agnathans. In addition, the vertebrae of agnathans possess several unique features, such as elastin-like molecules as the main matrix component and late (post-metamorphosis) differentiation of lamprey vertebrae. In this study, by tracing the developmental process of vertebrae in lamprey, we examined the homology of vertebrae between lampreys and gnathostomes. RESULTS: We found that the lamprey somite is first subdivided mediolaterally, with myotome cells differentiating medially and non-myotome cells emerging laterally...

The sclerotome in vertebrates comprises an embryonic population of cellular progenitors that give rise to diverse adult tissues including the axial skeleton, ribs, intervertebral discs, connective tissue, and vascular smooth muscle. In the thorax, this cell population arises in the ventromedial region of each of the segmented tissue blocks known as somites. How and when sclerotome adult tissue fates are specified and how the gene signatures that predate those fates are regulated has not been well studied. We have identified a previously unknown role for Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) in regulating sclerotome patterning in zebrafish...

Chiari III malformation is considered to be a rare congenital abnormality in human with very high mortality rates. Seventy percent of Chiari III is found to be associated with C1 arch defect as reported by Cakirer (Clin Imaging 27:1-4, 2003). The herniation of posterior fossa elements or dysplastic neural tissue is a must to stamp it as Chiari 3 malformation. The malformation is a result of the abnormal development of craniovertebral junction (CVJ). The CVJ developed from the occipital somites and the first spinal sclerotome...

The earliest skeletal muscle progenitor cells (SMPCs) derived from human pluripotent stem cells (hPSCs) are often identified by factors expressed by a diverse number of progenitors. An early transcriptional checkpoint that defines myogenic commitment could improve hPSC differentiation to skeletal muscle. Analysis of several myogenic factors in human embryos and early hPSC differentiations found SIX1+PAX3+ co-expression was most indictive of myogenesis. Using dCas9-KRAB hPSCs, we demonstrate that early inhibition of SIX1 alone significantly decreased PAX3 expression, reduced PAX7+ SMPCs, and myotubes later in differentiation...

Ciliopathies are associated with wide spectrum of structural birth defects (SBD), indicating important roles for cilia in development. Here we provide novel insights into the temporospatial requirement for cilia in SBDs arising from deficiency in Ift140 , an intraflagellar transport protein regulating ciliogenesis. Ift140 deficient mice exhibit cilia defects accompanied by wide spectrum of SBDs including macrostomia (craniofacial defects), exencephaly, body wall defects, tracheoesophageal fistula, randomized heart looping, congenital heart defects (CHD), lung hypoplasia, renal anomalies, and polydactyly...

The vertebrate spine is a metameric structure composed of alternating vertebral bodies (centra) and intervertebral discs.1 Recent studies in zebrafish have shown that the epithelial sheath surrounding the notochord differentiates into alternating cartilage-like (col2a1/col9a2+) and mineralizing (entpd5a+) segments which serve as a blueprint for centra formation.2 , 3 , 4 , 5 This process also defines the trajectories of migrating sclerotomal cells that form the mature vertebral bodies.4 Previous work demonstrated that notochord segmentation is typically sequential and involves the segmented activation of Notch signaling...