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The International Journal of... 2021The axial skeleton of the has undergone an evolutionary reduction of its bone elements. This structural plan is strongly preserved throughout the order and would have... (Review)
Review
The axial skeleton of the has undergone an evolutionary reduction of its bone elements. This structural plan is strongly preserved throughout the order and would have emerged as a highly specialized anatomical adaptation to its locomotor jumping pattern. The development programs that direct the vertebral morphogenesis of the anurans are poorly described and the molecular bases that have caused their pattern to differ from other tetrapods are completely unknown. In this work, we review the ontogeny of the spinal column of the anurans and explore the genetic mechanisms that could explain the morphological difference and the maintenance of the body plan during evolution. Here, we propose that the absence of caudal osseous elements, as a consequence of the inability of sclerotomes to form cartilaginous condensations in frogs, could be due to changes in both pattern and expression levels of , , and genes along the anteroposterior axis. The anteriorised expression of the genes together with the reduction in the expression levels of , and in the posterior somites could explain, at least partly, the loss of caudal vertebrae in the anurans during evolution.
Topics: Animals; Anura; Bone and Bones; Gene Expression Regulation, Developmental; Genes, Homeobox; Skeleton; Somites
PubMed: 32930370
DOI: 10.1387/ijdb.200230ss -
Orthopaedics & Traumatology, Surgery &... Feb 2023Malformations of the cervical spine are a challenge in pediatric orthopedic surgery since the treatment options are limited. These congenital anomalies are often... (Review)
Review
Malformations of the cervical spine are a challenge in pediatric orthopedic surgery since the treatment options are limited. These congenital anomalies are often syndrome-related and have multiple repercussions on the function and statics of the cervical spine in all three planes. They are related to developmental abnormalities during the somite segmentation that occurs during the third week of embryonic development. Successful somitogenesis requires proper functioning of a clock regulated by complex signaling pathways that guide the steps needed to form the future spine. There is no specific classification for vertebral malformations at the cervical level. To characterize the progressive nature of a malformation, one must use general classifications. In the specific case of Klippel-Feil syndrome, these malformations can affect several vertebral levels in a continuous or discontinuous manner, but also the vertebral body and vertebral arch in a variable way. Thus, establishing a reliable prognosis in the coronal and sagittal planes is a complex undertaking. While technical mastery of certain osteotomy procedures has led to advances in the surgical treatment of rigid deformities of the cervical spine, the indications are still very rare. Nevertheless, the procedure has become safer and more accurate because of technical aids such as surgical navigation, robotics and 3D printed models or patient-specific guides. Occipitocervical transitional anomalies have embryological specificities that can explain the bony malformations seen at this level. However, most are rare, and the main concern is identifying any instability that justifies surgical stabilization. The presence of a cervical spine anomaly should trigger the search for occipitocervical instability and vice-versa.
Topics: Child; Humans; Klippel-Feil Syndrome; Cervical Vertebrae; Spinal Diseases
PubMed: 36302448
DOI: 10.1016/j.otsr.2022.103459 -
Cellular and Molecular Life Sciences :... Feb 2021During embryogenesis, the processes that control how cells differentiate and interact to form particular tissues and organs with precise timing and shape are of... (Review)
Review
During embryogenesis, the processes that control how cells differentiate and interact to form particular tissues and organs with precise timing and shape are of fundamental importance. One prominent example of such processes is vertebrate somitogenesis, which is governed by a molecular oscillator called the segmentation clock. The segmentation clock system is initiated in the presomitic mesoderm in which a set of genes and signaling pathways exhibit coordinated spatiotemporal dynamics to establish regularly spaced boundaries along the body axis; these boundaries provide a blueprint for the development of segment-like structures such as spines and skeletal muscles. The highly complex and dynamic nature of this in vivo event and the design principles and their regulation in both normal and abnormal embryogenesis are not fully understood. Recently, live-imaging has been used to quantitatively analyze the dynamics of selected components of the circuit, particularly in combination with well-designed experiments to perturb the system. Here, we review recent progress from studies using live imaging and manipulation, including attempts to recapitulate the segmentation clock in vitro. In combination with mathematical modeling, these techniques have become essential for disclosing novel aspects of the clock.
Topics: Biological Clocks; Body Patterning; Cell Differentiation; Embryonic Development; Gene Expression Regulation, Developmental; Humans; Mesoderm; Models, Theoretical; Signal Transduction; Somites
PubMed: 33015720
DOI: 10.1007/s00018-020-03655-z -
Frontiers in Cell and Developmental... 2021Somitogenesis refers to the segmentation of the paraxial mesoderm, a tissue located on the back of the embryo, into regularly spaced and sized pieces, i.e., the somites.... (Review)
Review
Somitogenesis refers to the segmentation of the paraxial mesoderm, a tissue located on the back of the embryo, into regularly spaced and sized pieces, i.e., the somites. This periodicity is important to assure, for example, the formation of a functional vertebral column. Prevailing models of somitogenesis are based on the existence of a gene regulatory network capable of generating a striped pattern of gene expression, which is subsequently translated into periodic tissue boundaries. An alternative view is that the pre-pattern that guides somitogenesis is not chemical, but of a mechanical origin. A striped pattern of mechanical strain can be formed in physically connected tissues expanding at different rates, as it occurs in the embryo. Here we argue that both molecular and mechanical cues could drive somite periodicity and suggest how they could be integrated.
PubMed: 34901002
DOI: 10.3389/fcell.2021.753446 -
Advances in Clinical and Experimental... Apr 2020The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also known as Müllerian agenesis or aplasia, is a congenital disease manifested by the aplasia of the uterus and... (Review)
Review
The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also known as Müllerian agenesis or aplasia, is a congenital disease manifested by the aplasia of the uterus and the upper 2/3 of the vagina; its incidence is 1 in 4,000-5,000 female live births. We can distinguish 2 types of the MRKH syndrome: type I, which is characterized by an isolated absence of 2/3 of the vagina and uterus; and type II or MURCS (Müllerian duct aplasia, unilateral renal agenesis and cervicothoracic somite anomalies), which is also associated with other symptoms. The treatment of the MRKH syndrome patients aims at creating a neovagina and enabling sexual intercourse. Non-surgical techniques are the first-choice methods, and more than 90% of patients notice an anatomical and functional improvement if they are well-prepared emotionally. If non-surgical treatment does not bring about the expected results, a surgical procedure remains an option. The surgical method is mainly determined by the surgeon's experience. There are a few types of operations, though none of them seems superior to others. The next challenge is to provide these patients with a chance to become parents. Nowadays, a uterine transplant, a surrogate or adoption are the available solutions. An interdisciplinary approach is required, and the treatment should consist of medical and psychological support. This review presents the current knowledge about the MRKH syndrome with regard to the current methods of non-surgical and surgical treatment as well as a summary of the associated psychological problems.
Topics: 46, XX Disorders of Sex Development; Congenital Abnormalities; Female; Humans; Mullerian Ducts; Uterus; Vagina
PubMed: 32348039
DOI: 10.17219/acem/118850 -
Frontiers in Cell and Developmental... 2023Morphological phenotyping of the mouse embryo is described at neurulation stages, primarily as a guide to evaluating the outcome of whole embryo cultures between... (Review)
Review
Morphological phenotyping of the mouse embryo is described at neurulation stages, primarily as a guide to evaluating the outcome of whole embryo cultures between embryonic days 8.5 and 9.5. During this period, neural tube closure is initiated and progresses to completion in the cranial region. Spinal closure is still underway at the end of the culture period. The focus of this article is particularly on phenotyping that can be performed at the bench, using a stereomicroscope. This involves assessment of embryonic health, through observation and scoring of yolk sac blood circulation, measurement of developmental stage by somite counting, and determination of crown-rump length as a measure of growth. Axial rotation ("turning") can also be assessed using a simple scoring system. Neural tube closure assessment includes: 1) determining whether closure has been initiated at the Closure 1 site; 2) evaluating the complex steps of cranial neurulation including initiation at Closure sites 2 and 3, and completion of closure at the anterior and hindbrain neuropores; 3) assessment of spinal closure by measurement of posterior neuropore length. Interpretation of defects in neural tube closure requires an appreciation of, first, the stages that particular events are expected to be completed and, second, the correspondence between embryonic landmarks, for example, somite position, and the resulting adult axial levels. Detailed embryonic phenotyping, as described in this article, when combined with the versatile method of whole embryo culture, can form the basis for a wide range of experimental studies in early mouse neural development.
PubMed: 37601098
DOI: 10.3389/fcell.2023.1223849 -
Cells & Development Dec 2021Vertebrate segmentation, the process that generates a regular arrangement of somites and thereby establishes the pattern of the adult body and of the musculoskeletal and... (Review)
Review
Vertebrate segmentation, the process that generates a regular arrangement of somites and thereby establishes the pattern of the adult body and of the musculoskeletal and peripheral nervous systems, was noticed many centuries ago. In the last few decades, there has been renewed interest in the process and especially in the molecular mechanisms that might account for its regularity and other spatial-temporal properties. Several models have been proposed but surprisingly, most of these do not provide clear links between the molecular mechanisms and the cell behaviours that generate the segmental pattern. Here we present a short survey of our current knowledge about the cellular aspects of vertebrate segmentation and the similarities and differences between different vertebrate groups in how they achieve their metameric pattern. Taking these variations into account should help to assess each of the models more appropriately.
Topics: Animals; Body Patterning; Somites; Vertebrates
PubMed: 34391979
DOI: 10.1016/j.cdev.2021.203732 -
Mechanisms of Development Sep 2020The Brachyury gene encodes a transcription factor that is conserved across all animals. In non-chordate metazoans, brachyury is primarily expressed in ectoderm regions... (Review)
Review
The Brachyury gene encodes a transcription factor that is conserved across all animals. In non-chordate metazoans, brachyury is primarily expressed in ectoderm regions that are added to the endodermal gut during development, and often form a ring around the site of endoderm internalization in the gastrula, the blastopore. In chordates, this brachyury ring is conserved, but the gene has taken on a new role in the formation of the mesoderm. In this phylum, a novel type of mesoderm that develops into notochord and somites has been added to the ancestral lateral plate mesoderm. Brachyury contributes to a shift in cell fate from neural ectoderm to posterior notochord and somites during a major lineage segregation event that in Xenopus and in the zebrafish takes place in the early gastrula. In the absence of this brachyury function, impaired formation of posterior mesoderm indirectly affects the gastrulation movements of peak involution and convergent extension. These movements are confined to specific regions and stages, leaving open the question why brachyury expression in an extensive, coherent ring, before, during and after gastrulation, is conserved in the two species whose gastrulation modes differ considerably, and also in many other metazoan gastrulae of diverse structure.
Topics: Animals; Ectoderm; Endoderm; Fetal Proteins; Gastrula; Mesoderm; Morphogenesis; Notochord; T-Box Domain Proteins; Xenopus laevis; Zebrafish
PubMed: 32526279
DOI: 10.1016/j.mod.2020.103625 -
Nature Genetics Mar 2022Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, a single-cell zygote gives rise to millions of cells...
Mammalian embryogenesis is characterized by rapid cellular proliferation and diversification. Within a few weeks, a single-cell zygote gives rise to millions of cells expressing a panoply of molecular programs. Although intensively studied, a comprehensive delineation of the major cellular trajectories that comprise mammalian development in vivo remains elusive. Here, we set out to integrate several single-cell RNA-sequencing (scRNA-seq) datasets that collectively span mouse gastrulation and organogenesis, supplemented with new profiling of ~150,000 nuclei from approximately embryonic day 8.5 (E8.5) embryos staged in one-somite increments. Overall, we define cell states at each of 19 successive stages spanning E3.5 to E13.5 and heuristically connect them to their pseudoancestors and pseudodescendants. Although constructed through automated procedures, the resulting directed acyclic graph (TOME (trajectories of mammalian embryogenesis)) is largely consistent with our contemporary understanding of mammalian development. We leverage TOME to systematically nominate transcription factors (TFs) as candidate regulators of each cell type's specification, as well as 'cell-type homologs' across vertebrate evolution.
Topics: Animals; Embryo, Mammalian; Embryonic Development; Gastrulation; Mammals; Mice; Organogenesis
PubMed: 35288709
DOI: 10.1038/s41588-022-01018-x -
Seminars in Cell & Developmental Biology Nov 2020The body axis of vertebrates is subdivided into repetitive compartments called somites, which give rise primarily to the segmented architecture of the musculoskeletal... (Review)
Review
The body axis of vertebrates is subdivided into repetitive compartments called somites, which give rise primarily to the segmented architecture of the musculoskeletal system in the adult body. Somites form in a sequential and rhythmic manner in embryos and a physical boundary separates each somite from the rest of the unsegmented tissue and adjoining somites. Precise positioning of somite boundaries and determination of boundary cell fate in a select group of cells is thought to be driven by gene expression patterns and morphogen gradients. This pre-patterning step is followed by a mechanical process involving actomyosin activation in boundary cells and formation of an extracellular matrix that results in morphological boundary formation. While genes involved in somite boundary formation have been identified, there are many open questions about the underlying pre-patterning dynamics and mechanics and how these processes are coupled to generate a morphological boundary. Here, focusing on segmentation of zebrafish embryos as a model, we review pre-patterning processes critical for boundary formation and how cytoskeletal activity drives tissue separation. Our outlook is that this system holds exciting new avenues for unearthing general principles of boundary formation in developing embryos.
Topics: Animals; Biological Evolution; Body Patterning; Embryo, Nonmammalian; Models, Biological; Somites; Zebrafish
PubMed: 32444288
DOI: 10.1016/j.semcdb.2020.04.014