AUTHOR=Xu Xin , Miller Eric C. , Pozzo-Miller Lucas 

TITLE=Dendritic spine dysgenesis in Rett syndrome

JOURNAL=Frontiers in Neuroanatomy

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2014.00097

DOI=10.3389/fnana.2014.00097

ISSN=1662-5129

ABSTRACT=<p>Spines are small cytoplasmic extensions of dendrites that form the postsynaptic compartment of the majority of excitatory synapses in the mammalian brain. Alterations in the numerical density, size, and shape of dendritic spines have been correlated with neuronal dysfunction in several neurological and neurodevelopmental disorders associated with intellectual disability, including Rett syndrome (RTT). RTT is a progressive neurodevelopmental disorder associated with intellectual disability that is caused by loss of function mutations in the transcriptional regulator methyl CpG-binding protein 2 (<italic>MECP2</italic>). Here, we review the evidence demonstrating that principal neurons in RTT individuals and <italic>Mecp2</italic>-based experimental models exhibit alterations in the number and morphology of dendritic spines. We also discuss the exciting possibility that signaling pathways downstream of brain-derived neurotrophic factor (BDNF), which is transcriptionally regulated by MeCP2, offer promising therapeutic options for modulating dendritic spine development and plasticity in RTT and other <italic>MECP2</italic>-associated neurodevelopmental disorders.</p>