Thyroid Hormone Action in Cerebellum and Cerebral Cortex Development

Thyroid hormones (TH, including the prohormone thyroxine (T4) and its active deiodinated derivative 3,3′,5-triiodo-L-thyronine (T3)) are important regulators of vertebrates neurodevelopment. Specific transporters and deiodinases are required to ensure T3 access to the developing brain. T3 activates a number of differentiation processes in neuronal and glial cell types by binding to nuclear receptors, acting directly on transcription. Only few T3 target genes are currently known. Deeper investigations are urgently needed, considering that some chemicals present in food are believed to interfere with T3 signaling with putative neurotoxic consequences

Water vapor Raman-lidar observations from multiple sites in the framework of WaLiNeAs

During the Water Vapor Lidar Network Assimilation (WaLiNeAs) campaign, 8 lidars specifically designed to measure water vapor mixing ratio (WVMR) profiles were deployed on the western Mediterranean coast. The main objectives were to investigate the water vapor content during case studies of heavy precipitation events in the coastal Western Mediterranean and assess the impact of high spatio-temporal WVMR data on numerical weather prediction forecasts by means of state–of–the–art assimilation techniques. Given the increasing occurrence of extreme events due to climate change, WaLiNeAs is the first program in Europe to provide network–like, simultaneous and continuous water vapor profile measurements. This paper focuses on the WVMR profiling datasets obtained from three of the lidars managed by the French component of the WaLiNeAs team. These lidars were deployed in the towns of Coursan, Grau du Roi and Cannes. This measurement setup enabled monitoring of the water vapor content within the low troposphere along a period of three months over autumn – winter 2022 and four months in summer 2023. The lidars measured the WVMR profiles from the surface up to approximately 6–10 km at night, and 1–2 km during daytime; with a vertical resolution of 100 m and a time sampling between 15 – 30 min, selected to meet the needs of weather forecasting with an uncertainty lower than 0.4 g kg-1. The paper presents details about the instruments, the experimental strategy, as well as the datasets given in NETcdf format. The final dataset is divided in two datasets, the first with a time resolution of 15 min, which contains a total of 26 423 WVMR vertical profiles and the second with a time resolution of 30 min to improve the signal to noise ratio and signal altitude range

Heterogeneity of variance components for preweaning growth in Romane sheep due to the number of lambs reared

<p>Abstract</p> <p>Background</p> <p>The pre-weaning growth rate of lambs, an important component of meat market production, is affected by maternal and direct genetic effects. The French genetic evaluation model takes into account the number of lambs suckled by applying a multiplicative factor (1 for a lamb reared as a single, 0.7 for twin-reared lambs) to the maternal genetic effect, in addition to including the birth*rearing type combination as a fixed effect, which acts on the mean. However, little evidence has been provided to justify the use of this multiplicative model. The two main objectives of the present study were to determine, by comparing models of analysis, 1) whether pre-weaning growth is the same trait in single- and twin-reared lambs and 2) whether the multiplicative coefficient represents a good approach for taking this possible difference into account.</p> <p>Methods</p> <p>Data on the pre-weaning growth rate, defined as the average daily gain from birth to 45 days of age on 29,612 Romane lambs born between 1987 and 2009 at the experimental farm of La Sapinière (INRA-France) were used to compare eight models that account for the number of lambs per dam reared in various ways. Models were compared using the Akaike information criteria.</p> <p>Results</p> <p>The model that best fitted the data assumed that 1) direct (maternal) effects correspond to the same trait regardless of the number of lambs reared, 2) the permanent environmental effects and variances associated with the dam depend on the number of lambs reared and 3) the residual variance depends on the number of lambs reared. Even though this model fitted the data better than a model that included a multiplicative coefficient, little difference was found between EBV from the different models (the correlation between EBV varied from 0.979 to 0.999).</p> <p>Conclusions</p> <p>Based on experimental data, the current genetic evaluation model can be improved to better take into account the number of lambs reared. Thus, it would be of interest to evaluate this model on field data and update the genetic evaluation model based on the results obtained.</p

Otx2 Gene Deletion in Adult Mouse Retina Induces Rapid RPE Dystrophy and Slow Photoreceptor Degeneration

International audienceBACKGROUND: Many developmental genes are still active in specific tissues after development is completed. This is the case for the homeobox gene Otx2, an essential actor of forebrain and head development. In adult mouse, Otx2 is strongly expressed in the retina. Mutations of this gene in humans have been linked to severe ocular malformation and retinal diseases. It is, therefore, important to explore its post-developmental functions. In the mature retina, Otx2 is expressed in three cell types: bipolar and photoreceptor cells that belong to the neural retina and retinal pigment epithelium (RPE), a neighbour structure that forms a tightly interdependent functional unit together with photoreceptor cells. METHODOLOGY/PRINCIPAL FINDINGS: Conditional self-knockout was used to address the late functions of Otx2 gene in adult mice. This strategy is based on the combination of a knock-in CreERT2 allele and a floxed allele at the Otx2 locus. Time-controlled injection of tamoxifen activates the recombinase only in Otx2 expressing cells, resulting in selective ablation of the gene in its entire domain of expression. In the adult retina, loss of Otx2 protein causes slow degeneration of photoreceptor cells. By contrast, dramatic changes of RPE activity rapidly occur, which may represent a primary cause of photoreceptor disease. CONCLUSIONS: Our novel mouse model uncovers new Otx2 functions in adult retina. We show that this transcription factor is necessary for long-term maintenance of photoreceptors, likely through the control of specific activities of the RPE

Genome-Wide Search Reveals the Existence of a Limited Number of Thyroid Hormone Receptor Alpha Target Genes in Cerebellar Neurons

Thyroid hormone (T3) has a major influence on cerebellum post-natal development. The major phenotypic landmark of exposure to low levels of T3 during development (hypothyroidism) in the cerebellum is the retarded inward migration of the most numerous cell type, granular neurons. In order to identify the direct genetic regulation exerted by T3 on cerebellar neurons and their precursors, we used microarray RNA hybridization to perform a time course analysis of T3 induced gene expression in primary cultures of cerebellar neuronal cell. These experiments suggest that we identified a small set of genes which are directly regulated, both in vivo and in vitro, during cerebellum post-natal development. These modest changes suggest that T3 does not acts directly on granular neurons and mainly indirectly influences the cellular interactions taking place during development

Thyroid hormone in brain and brain cells

Editorial.-- This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).Peer Reviewe

Regulation of T3 Availability in the Developing Brain: The Mouse Genetics Contribution

Alterations in maternal thyroid physiology may have deleterious consequences on the development of the fetal brain, but the underlying mechanisms remain elusive, hampering the development of appropriate therapeutic strategies. The present review sums up the contribution of genetically modified mouse models to this field. In particular, knocking out genes involved in thyroid hormone (TH) deiodination, transport, and storage has significantly improved the picture that we have of the economy of TH in the fetal brain and the underlying genetic program. These data pave the way for future studies to bridge the gap in knowledge between thyroid physiology and brain development

Effets physiologiques et pathogéniques de l aporécepteur de l hormone thyroïdienne alpha 1 au cours du développement de la souris

L hormone thyroïdienne (T3) a des fonctions pléiotropiques au cours du développement. Un déficit congénital de T3 est responsable d un retard mental sévère. Grâce à des souris possédant un transgène rapporteur, nous avons montré que l activité de l hormone est très hétérogène dans le cerveau pré et post-natal. T3 agit via les récepteurs nucléaires TR pour réguler la transcription de gènes-cibles. De nouveaux gènes-cibles ont été identifiés dans le cervelet post-natal, mais la cascade de signalisation demeure inconnue, en raison d interactions cellulaires complexes. Pour supprimer la réponse à T3 à un moment donné, dans une cellule donnée, des souris exprimant de façon conditionnelle un récepteur TR 1 muté ont été générées. Les mutants constitutifs ont un phénotype très proche de l hypothyroïdie, ce qui confirme l implication majeure du récepteur TR 1 non lié à T3 dans la pathogénie de l hypothyroïdie. Le système conditionnel permettra de disséquer le mécanisme d action de T3 in vivo.Thyroid hormone (T3) has pleiotropic functions during development. Congenital hypothyroidism results in severe mental retardation. Using transgenic reporter mice, we showed that T3 action is highly heterogeneous in pre and post-natal brain. The regulation of gene expression by T3 involves binding of the hormone to TR nuclear receptors acting as T3-dependant transcription factors. We identified new T3 direct target genes in postnatal cerebellum, but the T3 signaling cascade is still unknown, because of complexe cell cell interactions. To suppress T3 response in a specific cell type and at a specific time, we created new transgenic mice expressing a mutated TR?1 in a conditional manner. Constitutive mutants have a hypothyroid like phenotype. This confirms the importance of unliganded TR?1 receptor in hypothyroidism pathogenesis. The conditional system will permit to dissect in vivo T3 action.LYON-ENS Sciences (693872304) / SudocSudocFranceF

L'hormone thyroïdienne et ses récepteurs : la génétique de la souris clarifie-t-elle la situation ?

Chez les vertébrés, la forme active de l'hormone thyroïdienne (T3) agit directement sur la transcription en modifiant la conformation des récepteurs nucléaires TR (TRα1, TRβ1 et TRβ2) encodés par les gènes THRA et THRB. Ces récepteurs sont fixés sur l'ADN au niveau d'éléments de réponse spécifiques indépendamment de la présence d'hormone. La génétique de la souris a clarifié la fonction respective de chaque isoforme, déterminée en grande partie par le mode d'expression des gènes THRA et THRB. Elle a aussi révélé l'importance de l'action négative des TR en absence de ligand non seulement dans les conditions pathologiques que physiologique