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The importance of astrocyte heterogeneity came out as a hot topic in neurosciences especially over the last decades, when the development of new methodologies allowed demonstrating the existence of big differences in morphological, neurochemical and physiological features between astrocytes. However, although the knowledge about the biology of astrocytes is increasing rapidly, an important characteristic that remained unexplored, until the last years, has been the relationship between astrocyte lineages and cell heterogeneity. To fill this gap, a new method called StarTrack was recently developed, a powerful genetic tool that allows tracking astrocyte lineages forming cell clones. Using StarTrack, a single astrocyte progenitor and its progeny can be specifically labeled from its generation, during embryonic development, to its final fate in the adult brain. Because of this specific labeling, astrocyte clones, exhibiting heterogeneous morphologies and features, can be easily analyzed in relation to their ontogenetic origin. This review summarizes how astrocyte heterogeneity can be decoded studying the embryonic development of astrocyte lineages and their clonal relationship. Finally, we discuss about some of the challenges and opportunities emerging in this exciting area of investigation.

Astrocytes are a heterogeneous population of glial cells with multifaceted roles in the central nervous system. Recently, the new method for the clonal analysis Star Track evidenced the link between astrocyte heterogeneity and lineage. Here, we tested the morphological response to mechanical injury of clonally related astrocytes using the Star Track approach, which labels each cell lineage with a specific code of colors. Histological and immunohistochemical analyses at 7 days post injury revealed a variety of morphological changes that were different among distinct clones. In many cases, cells of the same clone responded equally to the injury, suggesting the dependence on their genetic codification (intrinsic response). However, in other cases cells of the same clone responded differently to the injury, indicating their response to extrinsic factors. Thus, whereas some clones exhibited a strong morphological alteration or a high proliferative response to the injury, other clones located at similar distances to the lesion were apparently unresponsive. Concurrence of different clonal responses to the injury reveals the importance of the development determining the astrocyte features in response to brain injuries. These features should be considered to develop therapies that affect glial function. © 2013 Martín-López et al.

( Abstrac)Olfaction is the most relevant chemosensory sense of the rodents. General odors are primarily detected by the main olfactory system while most pheromonal signals are received by the accessory olfactory system. The first relay in the brain occurs in the olfactory bulb, which is subdivided in the main and accessory olfactory bulb (MOB/AOB). Given that the cell generation time is different between AOB and MOB, and the cell characterization of AOB remains limited, the goal of this work was first, the definition of the layering of AOB/MOB and second, the determination of cellular phenotypes in the AOB in a time window corresponding to the early postnatal development. Moreover, since reelin (Reln) deficiency has been related to olfactory learning deficits, we analyzed reeler mice. First, we compared the layering between AOB and MOB at early embryonic stages. Then, cell phenotypes were established using specific neuronal and glial markers as well as the Reln adaptor protein Dab1 to analyse differences in both genetic backgrounds. There was no apparent difference in the cell phenotypes among AOB and MOB or between wild type (wt)and reeler animals. However, a disruption in the granular cell layer of reeler with respect to wt mice was observed. In conclusion, the AOB in Reln-deficient mice showed similar neuronal and glial cell types being only affected the organization of granular neurons. © Martín-López, Corona and L pez-Mascaraque.

Chitosan (Ch) and some of its derivatives have been proposed as good biomaterials for tissue engineering, to construct scaffolds promoting tissue regeneration. In this work we made composite films from Ch and mixtures of Ch with gelatin (G) and poly-l-lysine (PLL), and evaluated the growth on these films of PC12 and C6 lines as well as neurons and glial cells derived from cerebral tissue and dorsal root ganglia (DRG). C6 glioma cells proliferated on Ch, G, and Ch-+-G films, although metabolic activity was decreased by the presence of the G in the mixtures. NGF-differentiated PC12 cells, adhered preferentially on Ch and films containing PLL. Unlike NGF-treated PC12 cells, cortical and hippocampal neurons showed good adhesion to Ch and Ch-+-G films, where they extended neurites. Astrocytes adhered on Ch, Ch-+-G, and Ch-+-PLL mixtures, although viability decreased during the culture time. Olfactory ensheathing cells (OEC) adhered and proliferated to confluency on the wells covered with Ch-+-G films. Neurites from DRGs exhibited high extension on these films. These results demonstrate that Ch-+-G films have excellent adhesive properties for both neurons and regeneration-promoting glia (OEC). These films also promoted neurite extension from DRG, making them good candidates for tissue engineering of nerve repair. © The Author(s), 2010.

Biomaterial implants are a promising strategy to replace neural tissue that is lost after traumatic nerve damage. Chitosan (Ch) is a suitable material for nerve implantation when it is used at a minimum amount of 2% (w/v). The goal of this study was to determine the best mixture of 2% Ch with gelatin (G) and poly(L-lysine) (PLL) for use in neural tissue engineering. Using different physicochemical approaches we showed that all mixtures formed polyelectrolyte complexes with distinct electrostatic interactions between their compounds. This gave rise to different gel morphologies, among which Ch + G exhibited a significantly smaller pore size, unlike Ch + G + PLL. However, thermal resistance to degradation and the wettability of the Ch-based films were not affected. Additionally, these differences affected glial cells growth in long-term (14 days) cultures performed on Ch-based films. Astrocytes and olfactory ensheathing cells proliferated on G and Ch + G films which induced both flattened and spindle cell morphologies. Meanwhile, cortical and hippocampal neurons were similarly viable in all studied films and significantly lower than those observed in controls. Lastly, neurites from dorsal root ganglia extended the most on Ch + G films. These results show that a Ch + G mixture is a promising candidate for use in neural tissue engineering. © 2012 VSP.

The olfactory system represents one of the most suitable models to study interactions between the peripheral and central nervous systems. The developing olfactory epithelium (olfactory placode and pit) gives rise to several cell populations that migrate towards the telencephalic vesicle. One of these cell populations, called the Migratory Mass (MM), accompanies the first emerging olfactory axons from the olfactory placode, but the fate of these cells and their contribution to the Olfactory Bulb (OB) populations has not been properly addressed. To asses this issue we performed ultrasound-guided in utero retroviral injections at embryonic day (E) 11 revealing the MM as an early source of Olfactory Ensheathing Cells in later postnatal stages. Employing a wide number of antibodies to identify the nature of the infected cells we described that those cells generated within the MM at E11 belong to different cell populations both in the mesenchyma, where they envelop olfactory axons and express the most common glial markers, and in the olfactory bulb, where they are restricted to the Olfactory Nerve and Glomerular layers. Thus, the data reveal the existence of a novel progenitor class within the MM, potentially derived from the olfactory placode which gives rise to different neural cell population including some CNS neurons, glia and olfactory ensheathing cells. © 2010 Wiley-Liss, Inc.

Dab1 mediates reelin signalling and plays critical roles in early brain development such as the stereotypical positioning of neurons in the brain. The olfactory bulb undergoes a prominent layering reorganization, but shows not apparent differences between wild type and reeler in the layer organization. Therefore, an accurate regional and cellular simultaneous analysis of these molecules becomes essential to clarify the role played by Dab1 upon Reelin effect. The present study reveals a strong and consistent Dab1 mRNA and protein expressions, throughout the olfactory bulb layers in both wild type and reeler mice. In addition, noteworthy is the pattern of Dab1 location within cell nuclei in both strains. Furthermore, a temporal increment of Dab1 expression levels is detected from P0 to P15 in both strains, being the protein quantity higher in reeler than in wild type mice. Altogether, our results revealed that Reln acts directly from projection neurons via the production of different Reln fragments. Changes in the pattern of Dab1 expression could reflect an alternative Reln function in postnatal and adult stages, besides a possible regulation of Dab1 by other molecules distinct to Reln.