Mechanisms of robustness in gene regulatory networks involved in neural development

Abstract

The functions of living organisms are affected by different kinds of perturbation, both internal and external, which in many cases have functional effects and phenotypic impact. The effects of these perturbations become particularly relevant for multicellular organisms with complex body patterns and cell type heterogeneity, where transcriptional programs controlled by gene regulatory networks determine, for example, the cell fate during embryonic development. Therefore, an essential aspect of development in these organisms is the ability to maintain the functionality of their genetic developmental programs even in the presence of genetic variation, changing environmental conditions and biochemical noise, a property commonly termed robustness. We discuss the implication of different molecular mechanisms of robustness involved in neurodevelopment, which is characterized by the interplay of many developmental programs at a molecular, cellular and systemic level. We specifically focus on processes affecting the function of gene regulatory networks, encompassing transcriptional regulatory elements and post-transcriptional processes such as miRNA-based regulation, but also higher order regulatory organization, such as gene network topology. We also present cases where impairment of robustness mechanisms can be associated with neurodevelopmental disorders, as well as reasons why understanding these mechanisms should represent an important part of the study of gene regulatory networks driving neural development.