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4:1-11

Chapter 8

Events

Abstract

our understanding of the brain.

implicated on the inset of the disease.

functional genomics

1. Introduction

135

Systems Biology Perspectives for

Studying Neurodevelopmental

Elodie Mathieux and Marco Antonio Mendoza-Parra

Brain development follows a complex process orchestrated by diverse molecular and cellular events for which a perturbation can cause pathologies. In fact, multiple neuronal cell fate decisions driven by complex gene regulatory programs are involved in neurogenesis and neurodevelopment, and their characterization are part of the current challenges on neurobiology. In this chapter, we provide an overview of the various genomic strategies in use to explore the spatiotemporally defined gene regulatory wires implicated in brain development. Finally, we will discuss the intake of these approaches for understanding the multifactorial events implicated in neurodevelopment and the future requirements for further expanding

Keywords: neurogenesis, gene regulatory networks, cell fate, systems biology,

Since the release of the first draft of the human genome and the development of massive parallel DNA sequencing strategies, our understanding of the genetic basis for a variety of human illnesses, including neurological disease, has expanded rapidly. In fact, around 50% of the known Mendelian disorders were already matched with their underlined genes [1] and this gap is expected to further decrease, namely by the improvements in the analysis of non-coding genomic regions [2]. This being said, the performance on the identification of the genetic context of diseases with complex phenotypes is more modest, probably due to their multigenic etiology. In fact, the use of exome sequencing for the detection of new mutations in an

unknown gene in family pedigrees appeared as a straight approach in the context of Mendelian disorders, but at most it provides the list of common variants when applied to neurological illnesses with complex phenotypes. As a consequence, further functional genomic readouts, including transcriptomes, transcription factors profiling, or epigenetic landscaping, are required to further narrow the observed mutations and to reconstitute the complex relationship among the various genes

In this context, this chapter will focus on the use of such further readouts to complement previous exome sequencing efforts (for a review on the use of exome sequencing applied to neurological diseases: [3]) and provide an overview of the
