Tau's role in the developing brain: implications for intellectual disability

Abstract

Microdeletions encompassing the MAPT (Tau) locus resulting in intellectual disability raised the hypothesis that Tau may regulate early functions in the developing brain. Our results indicate that neuronal migration was inhibited in mouse brains following Tau reduction. In addition, the leading edge of radially migrating neurons was aberrant in spite of normal morphology of radial glia. Furthermore, intracellular mitochondrial transport and morphology were affected. In early postnatal brains, a portion of Tau knocked down neurons reached the cortical plate. Nevertheless, they exhibited far less developed dendrites and a striking reduction in connectivity evident by the size of boutons. Our novel results strongly implicate MAPT as a dosage-sensitive gene in this locus involved in intellectual disability. Furthermore, our results are likely to impact our understanding of other diseases involving Tau.

Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis

“…Strikingly, here we demonstrate that Tau depletion causes a transient alteration in the morphology of adult newborn neurons. Our data are consistent with those of previous reports showing a delayed morphological maturation of embryonic neurons both in vitro (Dawson et al , 2001) and in vivo (Sapir et al , 2012). Our results show that Tau knockout reduced the total dendritic length and branching of 4‐week‐old newborn granule neurons, a phenomenon not observed in 8‐week‐old newborn neurons.…”

“…Tau protein is crucial for the establishment of neuronal polarity during embryonic development, for axonal transport, and for the intracellular trafficking of various molecules (Caceres & Kosik, 1990; Dawson et al , 2001; de Barreda et al , 2010; Hernandez & Avila, 2010; Llorens‐Martin et al , 2011; Sapir et al , 2012). Given the tight control of Tau expression during AHN, it is reasonable to assume that this protein plays a regulatory role in this process.…”

Developmental neurotoxic effects of two pesticides: Behavior and neuroprotein studies on endosulfan and cypermethrin

“…Its primary function have been believed to involve the assembly and stabilization of microtubule (Weingarten et al, 1975) and to facilitate axonal transport (Dixit et al, 2008;Vila-Ortiz et al 2001). However, these may not be the most critical functions of tau and more implication points towards its possible involvement in cellular signaling, protein scaffolding and neuronal migration during development (Morris et al 2011;Sapir et al 2012). With the growing attention for tau, extensive studies with various transgenic models have been performed.…”

Synapse Assembly and Neurodevelopmental Disorders

“…MAPT promotes microtubule assembly and stability and may act as a linker protein between the microtubules and the plasma membrane. Thus, a reduction in MAPT can affect neuronal migration and deficits in dendritic arbor elaboration and synapse number (Sapir et al, 2012).…”