Tsai HH, Li H, Fuentealba LC, Molofsky AV, Taveira-Marques R, Zhuang H, Tenney A, Murnen AT, Fancy SP, Merkle F, Kessaris N, Alvarez-Buylla A, Richardson WD, Rowitch DH.
Regional Astrocyte Allocation Regulates CNS Synaptogenesis and Repair.
Science. 2012 Jun 28;
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This is indeed a very interesting paper, as it shows how different astrocytes are compared to oligodendrocytes—the latter migrating far and compensating for any cells that are lost, while the former stay put both during development and in adulthood.
In regard to astrocyte-induced disease, these findings may be relevant, as death of astrocytes in a given domain cannot be compensated for. However, the ablation experiments occur very early and may be less relevant to age-related neurodegenerative diseases.
I think the biggest progress will be to understand the region-specific differences and specialization these cells have, and, hence, understand how they are specialized to support the neurons in their domain.
This is one of the most interesting papers ever written on astrocytes. The implications are very important. Basically, it is showing that each domain of the brain has its own molecularly distinct type of astrocyte, and that these astrocytes respect their own unique boundaries. Most likely this is a very important design plan of the brain. It suggests distinct, domain-specific role(s) for astrocytes. Perhaps they are critical for specificity of axon guidance during development so appropriate neural circuit wiring occurs, as suggested by an earlier paper in Cell by David Anderson a few years ago (see Hochstim et al., 2008). Or perhaps they control domain-specific synapse formation, function, or plasticity. In addition, the paper also shows that killing of astrocytes in one domain results in a substantial decrease in excitatory synapse formation. A role for astrocytes in controlling synapse formation has so far mostly been shown in vitro, so it is very exciting to see evidence that astrocytes also have this role in vivo (see also previous work by Gabriel Corfas on the role of glia in synapse formation in the inner ear: also Rio et al., 2002).
This is a beautiful paper with many important implications, and it shows that we don't begin to understand the roles of astrocytes in normal development and function, and why so much glial heterogeneity is needed. There may be important implications for disease. Perhaps specific types of astrocytes malfunction or degenerate in disease situations. And, since astrocyte gene expression so closely resembles stem cells, perhaps domain-specific types of astrocytes can more easily be induced to become the type of neurons in that domain in order to repair/regenerate lost neuron types.
Hochstim C, Deneen B, Lukaszewicz A, Zhou Q, Anderson DJ.
Identification of positionally distinct astrocyte subtypes whose identities are specified by a homeodomain code.
Cell. 2008 May 2;133(3):510-22.
Rio C, Dikkes P, Liberman MC, Corfas G.
Glial fibrillary acidic protein expression and promoter activity in the inner ear of developing and adult mice.
J Comp Neurol. 2002 Jan 7;442(2):156-62.