4.6 Review

The chromatin basis of neurodevelopmental disorders: Rethinking dysfunction along the molecular and temporal axes

Journal

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2017.12.013

Keywords

-

Funding

  1. European Research Council (ERC) [DISEASEAVATARS 616441]
  2. Telethon Foundation [GGP13231B, GGP14265]
  3. Associazione Italiana per la Ricerca sul cancro (AIRC)
  4. Italian Ministry of Health (Ricerca Corrente Grant)
  5. ERANET-Neuron grant FoodForThought F4T from the Italian Ministry of Health
  6. EPIGEN Flagship Program of the Italian National Research Council (CNR)

Ask authors/readers for more resources

The complexity of the human brain emerges from a long and finely tuned developmental process orchestrated by the crosstalk between genome and environment. Vis a vis other species, the human brain displays unique functional and morphological features that result from this extensive developmental process that is, unsurprisingly, highly vulnerable to both genetically and environmentally induced alterations. One of the most striking outcomes of the recent surge of sequencing-based studies on neurodevelopmental disorders (NDDs) is the emergence of chromatin regulation as one of the two domains most affected by causative mutations or Copy Number Variations besides synaptic function, whose involvement had been largely predicted for obvious reasons. These observations place chromatin dysfunction at the top of the molecular pathways hierarchy that ushers in a sizeable proportion of NDDs and that manifest themselves through synaptic dysfunction and recurrent systemic clinical manifestation. Here we undertake a conceptual investigation of chromatin dysfunction in NDDs with the aim of systematizing the available evidence in a new framework: first, we tease out the developmental vulnerabilities in human corticogenesis as a structuring entry point into the causation of NDDs; second, we provide a much needed clarification of the multiple meanings and explanatory frameworks revolving around epigenetics, highlighting those that are most relevant for the analysis of these disorders; finally we go in-depth into paradigmatic examples of NDD-causing chromatin dysregulation, with a special focus on human experimental models and datasets.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available