Retinoic Acid-Dependent Signaling Pathways and Lineage Events in the Developing Mouse Spinal Cord

Studies in avian models have demonstrated an involvement of retinoid signaling in early neural tube patterning. The roles of this signaling pathway at later stages of spinal cord development are only partly characterized. Here we use Raldh2-null mouse mutants rescued from early embryonic lethality to study the consequences of lack of endogenous retinoic acid (RA) in the differentiating spinal cord. Mid-gestation RA deficiency produces prominent structural and molecular deficiencies in dorsal regions of the spinal cord. While targets of Wnt signaling in the dorsal neuronal lineage are unaltered, reductions in Fibroblast Growth Factor (FGF) and Notch signaling are clearly observed. We further provide evidence that endogenous RA is capable of driving stem cell differentiation. Raldh2 deficiency results in a decreased number of spinal cord derived neurospheres, which exhibit a reduced differentiation potential. Raldh2-null neurospheres have a decreased number of cells expressing the neuronal marker β-III-tubulin, while the nestin-positive cell population is increased. Hence, in vivo retinoid deficiency impaired neural stem cell growth. We propose that RA has separable functions in the developing spinal cord to (i) maintain high levels of FGF and Notch signaling and (ii) drive stem cell differentiation, thus restricting both the numbers and the pluripotent character of neural stem cells

Ascl1 as a novel player in the Ptf1a transcriptional network for GABAergic cell specification in the retina

In contrast with the wealth of data involving bHLH and homeodomain transcription factors in retinal cell type determination, the molecular bases underlying neurotransmitter subtype specification is far less understood. Using both gain and loss of function analyses in Xenopus, we investigated the putative implication of the bHLH factor Ascl1 in this process. We found that in addition to its previously characterized proneural function, Ascl1 also contributes to the specification of the GABAergic phenotype. We showed that it is necessary for retinal GABAergic cell genesis and sufficient in overexpression experiments to bias a subset of retinal precursor cells towards a GABAergic fate. We also analysed the relationships between Ascl1 and a set of other bHLH factors using an in vivo ectopic neurogenic assay. We demonstrated that Ascl1 has unique features as a GABAergic inducer and is epistatic over factors endowed with glutamatergic potentialities such as Neurog2, NeuroD1 or Atoh7. This functional specificity is conferred by the basic DNA binding domain of Ascl1 and involves a specific genetic network, distinct from that underlying its previously demonstrated effects on catecholaminergic differentiation. Our data show that GABAergic inducing activity of Ascl1 requires the direct transcriptional regulation of Ptf1a, providing therefore a new piece of the network governing neurotransmitter subtype specification during retinogenesis.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Dynamic MRI to quantify musculoskeletal motion: A systematic review of concurrent validity and reliability, and perspectives for evaluation of musculoskeletal disorders.

To report evidence for the concurrent validity and reliability of dynamic MRI techniques to evaluate in vivo joint and muscle mechanics, and to propose recommendations for their use in the assessment of normal and impaired musculoskeletal function.The search was conducted on articles published in Web of science, PubMed, Scopus, Academic search Premier, and Cochrane Library between 1990 and August 2017. Studies that reported the concurrent validity and/or reliability of dynamic MRI techniques for in vivo evaluation of joint or muscle mechanics were included after assessment by two independent reviewers. Selected articles were assessed using an adapted quality assessment tool and a data extraction process. Results for concurrent validity and reliability were categorized as poor, moderate, or excellent.Twenty articles fulfilled the inclusion criteria with a mean quality assessment score of 66% (±10.4%). Concurrent validity and/or reliability of eight dynamic MRI techniques were reported, with the knee being the most evaluated joint (seven studies). Moderate to excellent concurrent validity and reliability were reported for seven out of eight dynamic MRI techniques. Cine phase contrast and real-time MRI appeared to be the most valid and reliable techniques to evaluate joint motion, and spin tag for muscle motion.Dynamic MRI techniques are promising for the in vivo evaluation of musculoskeletal mechanics; however results should be evaluated with caution since validity and reliability have not been determined for all joints and muscles, nor for many pathological conditions