Biomolecular condensates are found throughout eukaryotic cells, including in the nucleus, in the cytoplasm and on membranes. They are also implicated in a wide range of cellular functions, organizing molecules that act in processes ranging from RNA metabolism to signalling to gene regulation. Early work in the field focused on identifying condensates and understanding how their physical properties and regulation arise from molecular constituents. Recent years have brought a focus on understanding condensate functions. Studies have revealed functions that span different length scales: from molecular (modulating the rates of chemical reactions) to mesoscale (organizing large structures within cells) to cellular (facilitating localization of cellular materials and homeostatic responses). In this Roadmap, we discuss representative examples of biochemical and cellular functions of biomolecular condensates from the recent literature and organize these functions into a series of non-exclusive classes across the different length scales. We conclude with a discussion of areas of current interest and challenges in the field, and thoughts about how progress may be made to further our understanding of the widespread roles of condensates in cell biology.

A framework for understanding the functions of biomolecular condensates across scales.

Ependym und Circumventriculäre Organe

https://www.cell.com/neuron/pdf/S0896-6273(00)80253-6.pdf

Synaptic Currents Generated by Neuronal Acetylcholine Receptors Sensitive to α-Bungarotoxin

The brain-specific S-100 protein was localized at the electron microscopic level in the anterior and posterior pituitary gland of adult rat by indirect immunoperoxidase histology. The protein was found in the stellate cells of the pars distalis and tuberalis, in the marginal cells that line the hypophyseal cleft and in the glia-like cells, the pituicytes, of the neural lobe. The pituicytes, the stellate cells and the marginal cells have in common at least two properties: they all express a brain-specific marker and they are satellite cells to the secretory axons in the neural lobe and of the secretory cells in the adenohypophysis. These properties suggest that the S-100 cells in the pituitary gland are neuroectodermal in origin, possibly glial in nature.

Immunocytochemical localization of the brain-specific S-100 protein in the pituitary gland of adult rat.

The Threshold Theory for Parkinson's Disease

✓ Spinal cord tissue was obtained from 13- and 14-day embryonic rats and homologously grafted to the completely transected spinal cord of adult rats. Eight and 12 weeks after grafting, clinical, electrophysiological, histological, and neuroanatomical studies were performed. Motor performance of the hosts was assessed by the inclined-plane test. The conduction of nerve impulses across the lesion-transplantation site was evaluated by recording the spinal corticomotor and somatosensory evoked potentials. The survival, growth, differentiation, and parenchymal integration of the graft were documented histologically on semi-thin sections. The axonal interactions between the host spinal cord and the graft as well as the posttraumatic retrograde degeneration of corticospinal axons were investigated using the horseradish peroxidase (HRP) technique. Clinical and electrophysiological assessments did not demonstrate any functional activity of the graft. On histological examination, grafted neurons showed a survival r...

Studies on embryonic transplants to the transected spinal cord of adult rats

The effects of acetyl-L-carnitine on some degenerative and regenerative phenomena following sciatic nerve transection in rats, were studied. In Experiment 1, acetyl-L-carnitine was administered intraperitoneally at the dose of 50 mg/kg/day for 28 and 56 days following transection and microsurgical repair of the sciatic nerve. On day 56, the acetyl-L-carnitine-treated rats showed a significantly (p less than 0.05) better motor recovery ("clinical assessment") of the peroneal component of the sciatic nerve than the control rats. Twenty-eight days after nerve repair, the acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of myelinated axons in the postlesional nerve stump than control rats. Finally, the treated rats had a significantly lower (p less than 0.05) presence of atrophic fibres in the extensor digitorum longus muscle. In Experiment 2 the sciatic nerve was cut. To prevent spontaneous regeneration, a metallic clip was applied to the distal nerve stump and then the nerve stumps were positioned in different anatomical compartments. After surgery, a group of rats was treated with acetyl-L-carnitine dissolved in the drinking water (75 mg/kg/day). Another group of rats received normal water and served as the control group. Three, 6, 9, 12 and 18 months postoperatively, in the rats of both groups, the proximal sciatic nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. While in untreated rats the number of horseradish peroxidase-labelled neurons decreased with the increase in denervation time, in acetyl-L-carnitine-treated rats the number of horseradish peroxidase-labelled neurons remained stable for as long as 12 months of denervation and decreased only after 18 months of denervation. Furthermore, acetyl-L-carnitine-treated rats showed a significantly higher (p less than 0.05) number of horseradish peroxidase-labelled neurons with respect to untreated rats both after 9 and 12 months of denervation. In Experiment 3, the sciatic nerve was cut and then repaired after periods of 3, 6, 9, 12, and 18 months. Four months after nerve repair, the sciatic nerve was again cut and the proximal nerve stump was injected with horseradish peroxidase to label the spinal cord neurons of the sciatic nerve nucleus. Both acetyl-L-carnitine-treated and untreated rats showed a tendency to have an increased number of horseradish peroxidase-labelled neurons with respect to intact rats of correspondent ages.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies on the degenerative and regenerative phenomena occurring after transection and repair of the sciatic nerve in rats: effects of acetyl-L-carnitine.

The purpose of this study is to investigate the ultrastructural features of perivascular cells as found in the neural lobe of the hypophysis. In particular, an inquiry was made into the nature of the relationship of such cells to neurosecretory fibers and endings. The latter, in fact, are often invaginated within the perivascular cells and enveloped by their processes; furthermore, they often reveal a certain number of empty granules as well as characteristics of degenerative nature. In the course of this study the localization of the perivascular cells has been investigated as well as that of their processes within the extensive interlobular network typical of the hypophysial neural lobe of rodents. Based on the data gathered, the hypothesis is put forward that the perivascular cells play an important role in the turnover of neurosecretory endings, both under physiological and experimental conditions, contributing thereby to the release of post-hypophysial hormones.

On the fine structure of the perivascular cells in the neural lobe of rats.

In adult guinea pigs, the oculomotor nerve was sectioned proximally (at the tentorial edge) or more distally (at the orbital fissure) and immediately repaired by reapproximation. During a 24-week postoperative period, extrinsic eye motility was assessed by analyzing the vestibulo-ocular reflexes. The regenerated oculomotor nerve was studied morphometrically on semi-thin histological sections at 16 and 24 weeks postinjury. The selectivity of muscle reinnervation was investigated by injection of both single (horseradish peroxidase) and double (fluorescent dyes) retrograde axonal tracers into the eye muscles. Following proximal repair of the oculomotor nerve, the degree of recovery of extraocular motility varied among different animals and remained stable over long-term observations. In animals with poor recovery, aberrant eye movements were always found, and the somatotopic map of the reinnervated eye muscles was greatly altered. Distortions of the central representation were also seen in those animals in which a good level of functional recovery was seen. However, in animals with good recovery, a topographic bias was re-established by about 65% of the original neuronal population, as opposed to 26% in the animals with poor recovery. Neurons located contralateral to the axotomized nucleus sprouted intra-axially and projected their axons to denervated eye muscles. The number and diameter of the regenerated axons, the number and soma diameter of the axotomized neurons, and the ratio of distal axonal branches to proximal supporting neurons were all related to the degree of functional recovery. Following repair of the oculomotor nerve at the orbital fissure, extraocular motility had recovered in all of the animals at 16 weeks without aberrant phenomena. Functional regeneration of the distally transected oculomotor nerve is thought to be the result of selective muscle reinnervation.

Experimental repair of the oculomotor nerve: the anatomical paradigms of functional regeneration.

Nella presente nota sono sinteticamente analizzati i caratteri ultrastrutturali dei pituiciti e, in particolare, i rapporti dei pituiciti stessi con le fibre neuro-secretorie spesso realizzantisi a livello dei prolungamenti pituicitari periferici, le zone di contatto interpituicitario ricche di complessi giunzionali e l'esistenza nel lobo neurale di cellule poco differenziate che potrebbero rappresentare i precursori dei pituiciti maturi.

C. Olivieri-Sangiacomo

Papers

Studies on embryonic transplants to the transected spinal cord of adult rats

Studies on the degenerative and regenerative phenomena occurring after transection and repair of the sciatic nerve in rats: effects of acetyl-L-carnitine.

On the fine structure of the perivascular cells in the neural lobe of rats.

Experimental repair of the oculomotor nerve: the anatomical paradigms of functional regeneration.

Ultrastructural features of pituicytes in the neural lobe of adult rats.