Astrocytes are an abundant and heterogeneous class of glial cells in the central nervous
system (CNS), and are known to play key roles in CNS development and homeostasis.
Consistent with these crucial roles, the malfunction of astrocytes is increasingly implicated in
the pathogenesis of injury and diseases of the CNS. However, how the development and
function of astrocytes are regulated on a molecular level, and how dysregulation of these
mechanisms contributes to CNS disorders, is still poorly understood.
During late embryonic and early postnatal development of the CNS, immature astrocytes are
generated by radial glial cells, the main progenitor cell type. While immature astrocytes
support brain development, e.g., by regulating axonal outgrowth and synapse formation,
mature astrocytes lose these developmental functions, but gain essential functions for
maintaining homeostasis in the adult CNS. For example, mature astrocytes control neuronal
energy supply and blood-brain barrier permeability. Furthermore, as a functional element of
“tripartite synapses” along with presynaptic and postsynaptic neurons, astrocytes are
capable of sensing and modulating synaptic transmission.
In injury and various CNS disorders, including common neurodegenerative disorders such as
Alzheimer’s disease, astrocytes become “reactive”, a complex, heterogenous response
which, dependent on the context, can either promote or ameliorate pathogenesis. Reactive
astrocytes can acquire a pro-inflammatory phenotype and lose mature homeostatic
functions, which can contribute to disease and injury pathogenesis, but they can also re-gain
developmental functions that may support CNS repair and regeneration. Increasing evidence
also suggests that defects in astrocyte development and their developmental support
functions may contribute to neurodevelopmental disorders, such as Rett Syndrome and
Schizophrenia.
Despite research over the last 25 years that has identified various extrinsic signals,
transcriptional factors and epigenetic mechanisms regulating astrocyte differentiation and
function, the gene regulatory programs that govern astrocyte specification and maturation
(astrogliogenesis) during CNS development, and their functional alterations during aging and
in response to pathology, remain poorly understood. Delineating and manipulating such
molecular mechanisms has the potential to reveal targets for biomedical interventions and
allow the development of strategies to combat CNS diseases associated with astrocyte
malfunction.
This Research Topic invites cutting-edge papers and reviews with a focus on the molecular
mechanisms that control the generation and function of astrocytes in CNS development,
homeostasis and disorders, such as:
- Transcriptional and epigenetic control of astrogliogenesis
- Transcriptional and epigenetic control of astrocyte heterogeneity
- Transcriptional and epigenetic control of astrocyte reactivity and plasticity in injury
- Extrinsic factors and signalling cascades regulating astrocyte development and
function
- Molecular mechanisms disrupting astrocyte functions in specific neurodevelopmental
and neurodegenerative disorders
Astrocytes are an abundant and heterogeneous class of glial cells in the central nervous
system (CNS), and are known to play key roles in CNS development and homeostasis.
Consistent with these crucial roles, the malfunction of astrocytes is increasingly implicated in
the pathogenesis of injury and diseases of the CNS. However, how the development and
function of astrocytes are regulated on a molecular level, and how dysregulation of these
mechanisms contributes to CNS disorders, is still poorly understood.
During late embryonic and early postnatal development of the CNS, immature astrocytes are
generated by radial glial cells, the main progenitor cell type. While immature astrocytes
support brain development, e.g., by regulating axonal outgrowth and synapse formation,
mature astrocytes lose these developmental functions, but gain essential functions for
maintaining homeostasis in the adult CNS. For example, mature astrocytes control neuronal
energy supply and blood-brain barrier permeability. Furthermore, as a functional element of
“tripartite synapses” along with presynaptic and postsynaptic neurons, astrocytes are
capable of sensing and modulating synaptic transmission.
In injury and various CNS disorders, including common neurodegenerative disorders such as
Alzheimer’s disease, astrocytes become “reactive”, a complex, heterogenous response
which, dependent on the context, can either promote or ameliorate pathogenesis. Reactive
astrocytes can acquire a pro-inflammatory phenotype and lose mature homeostatic
functions, which can contribute to disease and injury pathogenesis, but they can also re-gain
developmental functions that may support CNS repair and regeneration. Increasing evidence
also suggests that defects in astrocyte development and their developmental support
functions may contribute to neurodevelopmental disorders, such as Rett Syndrome and
Schizophrenia.
Despite research over the last 25 years that has identified various extrinsic signals,
transcriptional factors and epigenetic mechanisms regulating astrocyte differentiation and
function, the gene regulatory programs that govern astrocyte specification and maturation
(astrogliogenesis) during CNS development, and their functional alterations during aging and
in response to pathology, remain poorly understood. Delineating and manipulating such
molecular mechanisms has the potential to reveal targets for biomedical interventions and
allow the development of strategies to combat CNS diseases associated with astrocyte
malfunction.
This Research Topic invites cutting-edge papers and reviews with a focus on the molecular
mechanisms that control the generation and function of astrocytes in CNS development,
homeostasis and disorders, such as:
- Transcriptional and epigenetic control of astrogliogenesis
- Transcriptional and epigenetic control of astrocyte heterogeneity
- Transcriptional and epigenetic control of astrocyte reactivity and plasticity in injury
- Extrinsic factors and signalling cascades regulating astrocyte development and
function
- Molecular mechanisms disrupting astrocyte functions in specific neurodevelopmental
and neurodegenerative disorders