Birth and Rapid Subcellular Adaptation of a Hominoid-Specific CDC14 Protein

Gene duplication was prevalent during hominoid evolution, yet little is known about the functional fate of new ape gene copies. We characterized the CDC14B cell cycle gene and the functional evolution of its hominoid-specific daughter gene, CDC14Bretro. We found that CDC14B encodes four different splice isoforms that show different subcellular localizations (nucleus or microtubule-associated) and functional properties. A microtubular CDC14B variant spawned CDC14Bretro through retroposition in the hominoid ancestor 18–25 million years ago (Mya). CDC14Bretro evolved brain-/testis-specific expression after the duplication event and experienced a short period of intense positive selection in the African ape ancestor 7–12 Mya. Using resurrected ancestral protein variants, we demonstrate that by virtue of amino acid substitutions in distinct protein regions during this time, the subcellular localization of CDC14Bretro progressively shifted from the association with microtubules (stabilizing them) to an association with the endoplasmic reticulum. CDC14Bretro evolution represents a paradigm example of rapid, selectively driven subcellular relocalization, thus revealing a novel mode for the emergence of new gene function

Transcriptomic Signature of Human Embryonic Thyroid Reveals Transition From Differentiation to Functional Maturation

The human thyroid gland acquires a differentiation program as early as weeks 3–4 of embryonic development. The onset of functional differentiation, which manifests by the appearance of colloid in thyroid follicles, takes place during gestation weeks 10–11. By 12–13 weeks functional differentiation is accomplished and the thyroid is capable of producing thyroid hormones although at a low level. During maturation, thyroid hormones yield increases and physiological mechanisms of thyroid hormone synthesis regulation are established. In the present work we traced the process of thyroid functional differentiation and maturation in the course of human development by performing transcriptomic analysis of human thyroids covering the period of gestation weeks 7–11 and comparing it to adult human thyroid. We obtained specific transcriptomic signatures of embryonic and adult human thyroids by comparing them to non-thyroid tissues from human embryos and adults. We defined a non-TSH (thyroid stimulating hormone) dependent transition from differentiation to maturation of thyroid. The study also sought to shed light on possible factors that could replace TSH, which is absent in this window of gestational age, to trigger transition to the emergence of thyroid function. We propose a list of possible genes that may also be involved in abnormalities in thyroid differentiation and/or maturation, hence leading to congenital hypothyroidism. To our knowledge, this study represent the first transcriptomic analysis of human embryonic thyroid and its comparison to adult thyroid

Genes Expressed in Specific Areas of the Human Fetal Cerebral Cortex Display Distinct Patterns of Evolution

The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits

Travaux pratiques d'anatomie pathologique générale

3e édition 2001-02/1Vente uniquement aux étudiants suivant le cours susmentionné, sur présentation de leur carte d'étudiant MED3, DENT3, BIME3B, ANAT016info:eu-repo/semantics/published

Anatomie pathologique :travaux pratiques

ANAT 015info:eu-repo/semantics/published

Anatomie pathologique spéciale :Travaux pratiques

2e doctorat - ANAT 061info:eu-repo/semantics/published

Anatomie pathologique

ANAT 015info:eu-repo/semantics/published

Gynecomastie unilaterale chez un adolescent

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Collaboration and communities of practice in the field of medical ontology translation

This article provides insight into the collaborative translation of medical ontologies and how translators’ needs, commitment and desire to learn and share knowledge can be the seeds of a community of practice to support this type of translation. It is based on the experience of a project to translate 7,500 respiratory system concepts from SNOMED CT® into French. The project was guided by the following principles: (1) translators are bilingual medical experts in the field in which the terms to be translated are used; (2) linguistic advice is available during translation; (3) translating experts accept, correct or replace terms already translated by a web-based translation tool using a prepared lexicon. The project results were characterised by low acceptance of computer-assisted pre-translations due to inadequate lexicon preparation and insufficient alignment of the concepts to be translated with the expertise of the translating expert. These issues were solved to a considerable extent by web-based communication between translators, suggesting the need for well-structured collaboration between highly specialised field experts. Based on this observation, we discuss how a community of practice built on the motivation and needs of the translating experts could significantly support the quality and efficiency of medical ontology translation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe