Research Topic

Epigenetic Mechanisms of Neurogenesis in the Developing Neocortex

About this Research Topic

The term ‘epigenetics’ was coined in 1942 by Conrad H. Waddington, at a time when the underlying mechanisms were far from discovered. In his original definition, Waddington referred to ‘the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being’. Epigenetics has recently evolved from a collection of diverse phenomena that could not be explained by genetics to a well-defined field of study investigating the changes in gene expression that do not result from alteration in DNA sequence. Several systems, including modifications of DNA, histone modifications, chromatin remodeling and non-coding RNAs, are considered to initiate and sustain epigenetic change.

The neocortex is the seat of higher cognitive functions and is the most recently evolved part of the mammalian brain. During its evolution, the neocortex has expanded in several mammalian lineages, notable in humans, reflecting an increase in the number of neocortical neurons. The generation of cortical neurons during development is the result of proliferative and differentiative divisions of neural stem and progenitor cells, a process termed ‘neurogenesis’. Cell fate transitions are characterized by dynamic changes in gene expression that are conveyed by interactions between transcription factors and DNA in the context of chromatin. Chromatin carries multiple post-translational modifications that can be dynamically regulated by sets of enzymes that serve as ‘writers’ or ‘erasers’ to add or remove specific marks, and by ‘readers’ that recognize these modifications.

Tremendous efforts have been made in recent years to catalogue DNA and histone modifications in diverse cell lines and tissues. Indeed, some modifications, like DNA hydroxymethylation, seem particularly abundant in the mammalian brain. So far most mapping studies have used pieces of entire tissue compost of various different cell types. However, with recent advances in cell purification, the adaptation of chromatin immunoprecipitation protocols to small samples and single-cell sequencing techniques, the characterization of chromatin modifications and non-coding RNAs within individual progenitor cell types of complex tissues is in reach. Such cell type specific information will be crucial for our understanding of the role of epigenetic systems during stem cell decision making. Another exciting recent advance in epigenetic research is the development of epigenome editing techniques. While several chromatin proteins have already been shown in conventional knockout studies to play important roles during neurogenesis, technological advances now make it possible to interrogate selected individual single loci.

Taken together, there has been much excitement on epigenetic regulation during development and with this research topic, we would like to bring together exciting findings in the field of neurogenesis of the developing neocortex. We believe that with recent technological advances it will now be possible to tackle important open questions including: How does epigenetics contribute to neural stem cell decision making? How do chromatin and neural transcription factors interact to enable tight transcriptional control? And which regulatory sequences control neocortex development? The presented findings will not only advance our understanding of developmental neurogenesis, but will be relevant for instigations of the epigenetic basis of neurological and psychiatric disorders.


Keywords: Epigenetics, neurogenesis, development, neocortex, stem cell


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

The term ‘epigenetics’ was coined in 1942 by Conrad H. Waddington, at a time when the underlying mechanisms were far from discovered. In his original definition, Waddington referred to ‘the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being’. Epigenetics has recently evolved from a collection of diverse phenomena that could not be explained by genetics to a well-defined field of study investigating the changes in gene expression that do not result from alteration in DNA sequence. Several systems, including modifications of DNA, histone modifications, chromatin remodeling and non-coding RNAs, are considered to initiate and sustain epigenetic change.

The neocortex is the seat of higher cognitive functions and is the most recently evolved part of the mammalian brain. During its evolution, the neocortex has expanded in several mammalian lineages, notable in humans, reflecting an increase in the number of neocortical neurons. The generation of cortical neurons during development is the result of proliferative and differentiative divisions of neural stem and progenitor cells, a process termed ‘neurogenesis’. Cell fate transitions are characterized by dynamic changes in gene expression that are conveyed by interactions between transcription factors and DNA in the context of chromatin. Chromatin carries multiple post-translational modifications that can be dynamically regulated by sets of enzymes that serve as ‘writers’ or ‘erasers’ to add or remove specific marks, and by ‘readers’ that recognize these modifications.

Tremendous efforts have been made in recent years to catalogue DNA and histone modifications in diverse cell lines and tissues. Indeed, some modifications, like DNA hydroxymethylation, seem particularly abundant in the mammalian brain. So far most mapping studies have used pieces of entire tissue compost of various different cell types. However, with recent advances in cell purification, the adaptation of chromatin immunoprecipitation protocols to small samples and single-cell sequencing techniques, the characterization of chromatin modifications and non-coding RNAs within individual progenitor cell types of complex tissues is in reach. Such cell type specific information will be crucial for our understanding of the role of epigenetic systems during stem cell decision making. Another exciting recent advance in epigenetic research is the development of epigenome editing techniques. While several chromatin proteins have already been shown in conventional knockout studies to play important roles during neurogenesis, technological advances now make it possible to interrogate selected individual single loci.

Taken together, there has been much excitement on epigenetic regulation during development and with this research topic, we would like to bring together exciting findings in the field of neurogenesis of the developing neocortex. We believe that with recent technological advances it will now be possible to tackle important open questions including: How does epigenetics contribute to neural stem cell decision making? How do chromatin and neural transcription factors interact to enable tight transcriptional control? And which regulatory sequences control neocortex development? The presented findings will not only advance our understanding of developmental neurogenesis, but will be relevant for instigations of the epigenetic basis of neurological and psychiatric disorders.


Keywords: Epigenetics, neurogenesis, development, neocortex, stem cell


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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01 October 2017 Manuscript
01 January 2018 Manuscript Extension

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

01 October 2017 Manuscript
01 January 2018 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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