TY - JOUR T1 - Chromatin remodelling complexes in cerebral cortex development and neurodevelopmental disorders. JF - Neurochem Int Y1 - 2021 A1 - D'Souza, Leora A1 - Channakkar, Asha S A1 - Muralidharan, Bhavana AB -

The diverse number of neurons in the cerebral cortex are generated during development by neural stem cells lining the ventricle, and they continue maturing postnatally. Dynamic chromatin regulation in these neural stem cells is a fundamental determinant of the emerging property of the functional neural network, and the chromatin remodellers are critical determinants of this process. Chromatin remodellers participate in several steps of this process from proliferation, differentiation, migration leading to complex network formation which forms the basis of higher-order functions of cognition and behaviour. Here we review the role of these ATP-dependent chromatin remodellers in cortical development in health and disease and highlight several key mouse mutants of the subunits of the complexes which have revealed how the remodelling mechanisms control the cortical stem cell chromatin landscape for expression of stage-specific transcripts. Consistent with their role in cortical development, several putative risk variants in the subunits of the remodelling complexes have been identified as the underlying causes of several neurodevelopmental disorders. A basic understanding of the detailed molecular mechanism of their action is key to understating how mutations in the same networks lead to disease pathologies and perhaps pave the way for therapeutic development for these complex multifactorial disorders.

VL - 147 ER - TY - JOUR T1 - Understanding brain development - Indian researchers' past, present and growing contribution. JF - Int J Dev Biol Y1 - 2020 A1 - Muralidharan, Bhavana AB -

The brain is the seat of all higher-order functions in the body. Brain development and the vast array of neurons and glia it produces is a baffling mystery to be studied. Neuroscientists using a vast number of model systems have been able to crack many of the nitty-gritty details using various model systems. One way has been to size down the problem by utilizing the power of genetics using simple model systems such as Drosophila to create a fundamental framework in order to unravel the basic principles of brain development. Scientists have used simpler organisms to uncover the fundamental principles of brain development and also to study the evo-devo angle to brain development. Complex circuitry has been unraveled in complex model systems, such as the mouse, to reveal the intricacies and regional specialization of brain function. This is an ever-growing field, and with newer genetic and molecular tools, together with several new centers of excellence, India's contribution to this fascinating field of study is continually rising. Here, I review the pioneering work done by Indian developmental neurobiologists in the past and their mounting contribution in the present.

VL - 64 IS - 1-2-3 ER - TY - JOUR T1 - Relax, Don't RAN Translate It. JF - Neuron Y1 - 2019 A1 - Wilson, Katherine M A1 - Muralidharan, Bhavana A1 - Isaacs, Adrian M AB -

The (GGGGCC)n repeat expansion in C9orf72, which is the most common cause of frontotemporal dementia and amyotrophic lateral sclerosis, is translated through repeat-associated non-AUG (RAN) translation. In this issue of Neuron, Cheng et al. (2019) report that the helicase DDX3X, which unwinds (or relaxes) RNA, suppresses RAN translation and toxicity.

VL - 104 IS - 5 ER -