Publications by authors named "Sofia Zdral"

4 Publications

  • Page 1 of 1

Time-sequenced transcriptomes of developing distal mouse limb buds: A comparative tissue layer analysis.

Dev Dyn 2021 Jul 12. Epub 2021 Jul 12.

Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC (CSIC-University of Cantabria-SODERCAN), Santander, Spain.

Background: The development of the amniote limb has been an important model system to study patterning mechanisms and morphogenesis. For proper growth and patterning, it requires the interaction between the distal sub-apical mesenchyme and the apical ectodermal ridge (AER) that involve the separate implementation of coordinated and tissue-specific genetic programs.

Results: Here, we produce and analyze the transcriptomes of both distal limb mesenchymal progenitors and the overlying ectodermal cells, following time-coursed dissections that cover from limb bud initiation to fully patterned limbs. The comparison of transcriptomes within each layer as well as between layers over time, allowed the identification of specific transcriptional signatures for each of the developmental stages. Special attention was given to the identification of genes whose transcription dynamics suggest a previously unnoticed role in the context of limb development and also to signaling pathways enriched between layers.

Conclusion: We interpret the transcriptomic data in light of the known development pattern and we conclude that a major transcriptional transition occurs in distal limb buds between E9.5 and E10.5, coincident with the switch from an early phase continuation of the signature of trunk progenitors, related to the initial proximo distal specification, to a late intrinsic phase of development.
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July 2021

Spotted bones in an osteopoikilosis-related disease (Buschke Ollendorff Syndrome): Identifying this rare condition from the lab to the field.

Int J Paleopathol 2021 Sep 5;34:20-28. Epub 2021 Jun 5.

Department of Genetics, Instituto de Investigación Sanitaria, Hospital Universitario Fundación Jiménez Diaz, Avenida de los Reyes Católicos 2, 28040, Madrid, Spain. Electronic address:

Objective: To improve the differential diagnosis of osteopoikilosis in past populations using a clinical case as an example of this rare condition.

Materials: A patient referred to our Genetic Service with suspected Buschke Ollendorff Syndrome after finding a connective nevus.

Methods: Radiological images from different body regions were accompanied by a genetic study using next-generation sequencing.

Results: Small circular-to-ellipsoid sclerotic lesions were found in the epiphysis and metaphysis of long bones, as well as in the pelvis. These lesions were bilaterally distributed and with well-defined margins, compatible with the characteristics of Buschke Ollendorff Syndrome, bone manifestation osteopoikilosis. A heterozygous mutation on LEMD3 (NM_001167614:c.1918 + 1G > C) was identified by next-generation sequencing. Based on this confirmed case, we have discussed the most probable causes of similar bone lesions found in the archaeological record.

Conclusion: It has been demonstrated how a current case of a rare disease can provide useful tools to improve the differential diagnosis of this disease in ancient skeletons.

Significance: This work underlines the great need for multidisciplinary platforms that integrates clinical research into paleopathology in order to successfully address the study of rare diseases from the past.

Limitations: Since OPK is only detected by X-rays, suspected cases of this bone lesion will only be identified when radiographs are taken for other purposes.

Suggestions For Further Research: Retrospective and large-scale studies of radiographs from other research in past populations.
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September 2021

Elemental Composition in Female Dry Femora Using Portable X-Ray Fluorescence (pXRF): Association with Age and Osteoporosis.

Calcif Tissue Int 2021 Aug 1;109(2):231-240. Epub 2021 Apr 1.

Department of Life Sciences, Research Centre for Anthropology and Health (CIAS), University of Coimbra, Calçada Martim de Freitas, 3000-456, Coimbra, Portugal.

Pathophysiological conditions can modify the skeletal chemical concentration. This study analyzes the elemental composition in two anatomical regions from dry femoral bone using a portable X-Ray Fluorescence (pXRF) and evaluates its impact in the bone mineral density (BMD). The left femora of 97 female skeletons (21-95 years old individuals) from the Coimbra Identified Skeletal Collection were studied. Diagenetic biases were discarded at the outset and BMD was determined with Dual-energy X-ray absorptiometry. Chemical measurements were performed at the midpoint of the femoral neck and at the midshaft using a pXRF device, and comparisons were made considering the age and the BMD values. Only elements with a Technical Measurement Error ≤ 5% were selected: P, S, Ca, Fe, Zn, As, Sr, Pb and the Ca/P ratio. Statistically significant differences were found between regions, with higher concentrations of P, Ca, Zn and S at the midshaft, and the Ca/P ratio at the femoral neck. The concentration of P is higher in individuals < 50 years, while S and Ca/P ratio increase in individuals ≥ 50 years. The decrease of P with age can be simultaneously related to the decline of its concentration in osteoporosis. Decreased BMD is also associated with higher levels of S and Pb. Osteoporosis enhances the absorption of osteolytic elements in specific locations. This fast and non-destructive technique has proved effective for the comprehension of chemical changes related to bone mass loss. This study highlights the potential of identified skeletal collections to improve the knowledge about bone fragility.
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August 2021

Mammalian-specific ectodermal enhancers control the expression of genes in developing nails and hair follicles.

Proc Natl Acad Sci U S A 2020 12 16;117(48):30509-30519. Epub 2020 Nov 16.

Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas-Universidad de Cantabria-Sociedad para el Desarrollo de Cantabria, 39011 Santander, Spain;

Vertebrate genes are critical for the establishment of structures during the development of the main body axis. Subsequently, they play important roles either in organizing secondary axial structures such as the appendages, or during homeostasis in postnatal stages and adulthood. Here, we set up to analyze their elusive function in the ectodermal compartment, using the mouse limb bud as a model. We report that the gene cluster was co-opted to be transcribed in the distal limb ectoderm, where it is activated following the rule of temporal colinearity. These ectodermal cells subsequently produce various keratinized organs such as nails or claws. Accordingly, deletion of the cluster led to mice lacking nails (anonychia), a condition stronger than the previously reported loss of function of , which is the causative gene of the ectodermal dysplasia 9 (ECTD9) in human patients. We further identified two mammalian-specific ectodermal enhancers located upstream of the gene cluster, which together regulate gene expression in the hair and nail ectodermal organs. Deletion of these regulatory elements alone or in combination revealed a strong quantitative component in the regulation of genes in the ectoderm, suggesting that these two enhancers may have evolved along with the mammalian taxon to provide the level of HOXC proteins necessary for the full development of hair and nail.
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December 2020