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Biomedical subjects

B Llirbat

Publications and source records attributed to B Llirbat.

5 recordsLinked to original sources
PubMed1999

Positional specificities of retinal growth cones in the mouse superior colliculus.

In the developing retinotectal system, repulsive topographic tectal cues have been demonstrated to contribute to the final mapping. Here, we describe a novel response of nasal axons to growth-promoting cues expressed by anterior tectal cells. In in vitro experiments, contact of fibres from the nasal (but not temporal) pole of the mouse retina with anterior (but not posterior) tectal membranes leads to their adopting very elongated and filopodial morphologies, and to increase their growth rates. As previously demonstrated, fibres from the temporal pole of the retina are collapsed by posterior tectal membranes in vitro. In addition, a study of retinal growth cone morphologies in vivo, at early stages of target invasion, shows that growth cones of nasal fibres have streamlined morphologies, usually indicative of active elongation growth modes, in the anterior part of the embryonic mouse tectum, and more elaborate morphologies posteriorly. Vice versa, temporal fibres have mainly elaborate growth cones anteriorly, and collapsed growth cones posteriorly. These experiments demonstrate that nasal retinal fibres respond preferentially to permissive or growth-promoting cues in the embryonic mouse tectal environment, both in vitro and in vivo. This phenomenon might contribute to ingrowth of retinal fibres in their target area, and to promote the homing of nasal fibres towards the posterior aspect of the tectum, which is their normal target region.

Animals↗
PubMed1997

Normal and inhibited cholesterol synthesis in the cultured rat embryo.

The Smith-Lemli-Opitz syndrome-affected fetus presents a deficiency in delta7-dehydrocholesterol reductase, the last enzymatic step in the cholesterol biosynthesis pathway. Development of the abnormal human fetus takes place in a normal environment as the heterozygous mother's cholesterolemia remains normal. An animal model for this disease has been obtained from the offspring of pregnant rats treated with "distal" inhibitors of delta7-dehydrocholesterol reductase, AY-9944 or BM15766. In the animal model, embryonic development occurs in a disturbed environment characterized by hypocholesterolemia and accumulation of delta7-dehydrocholesterol and delta8-dehydrocholesterol in the maternal serum. The purpose of the present study was to assess, in cultured rat embryos at early developmental stages, the relative contributions of exogenous and de novo synthesized cholesterol in the total embryonic cholesterol, according to the conditions of normal and altered de novo biosynthesis. Cultured rat embryos are able to synthesize cholesterol as shown by 13C-incorporation into cholesterol from 13C-labeled precursors added to the culture medium. De novo cholesterol biosynthesis is altered by addition to the culture medium of AY-9944 which inhibits the delta7-dehydrocholesterol reductase and the delta8-delta7-sterol isomerase as suggested by the emergence of characteristic aberrant sterols in the embryonic tissues. Cholesterol-rich serum used for embryo culture alters the pattern in a way that confirms that the rat embryos are able to import exogenous cholesterol which down-regulates de novo cholesterol biosynthesis. Exogenous cholesterol substitutes for the deficit in a manner efficient enough to prevent the embryonic abnormalities induced by AY-9944.

Adaptation, Physiological↗
PubMed1997

[Cholesterol and development].

The teratogenic action of distal inhibitors of cholesterol synthesis has been known for some time. The induced malformations are of a particular type: they include holoprosencephalies. Recently these observations have solicited increased interest due to: 1/ the discovery in 1993 of a similar form of inhibition of cholesterol synthesis which is responsible for a human malformation syndrome, Smith-Lemli-Opitz; 2/ the demonstration of the involvement of the Sonic Hedgehog gene in normal development of prosencephalon and the description of the mode of action of the protein Shh: autoprocessing followed by "cholesterolisation".

Animals↗
PubMed1995

Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse.

Axonal navigation during development requires that cues present in the extracellular environment be capable of modifying the structure of the cone in a dynamic way. Protein kinase C (PKC) has long been suspected to be one of the multiple molecular relays present in the terminal structure of the developing axon and involved in the transduction of extracellular signals. The latter proposal is, however, based on the use of drugs or of protocols leading to pleiotropic and often nonspecific effects. In the present study, we have taken advantage of the discovery of a peptide capable of translocating across biological membranes and to accumulate in the cytoplasm and nucleus of cells in culture, to internalize a highly specific peptidic inhibitor of PKC. We demonstrate that linking the two peptides (vector and PKC inhibitor) allows the internalization of the latter in live cells, specifically inhibits PKC and provokes a rapid modification of growth cone morphology. This set of data thus establishes that a peptidic inhibitor of PKC activity, once internalized, provokes a change in growth cone morphology, reminiscent of the collapse phenotype. In addition, the present study describes a new efficient and harmless way to introduce pharmacologically active substances in neural cells in culture.

Amino Acid Sequence↗