Other Publication Details
Mandatory Fields
Reviews
Hegarty, SV;Sullivan, AM;O'Keeffe, GW
2015
September
Zeb2: A multifunctional regulator of nervous system development
Validated
1
WOS: 68 ()
Optional Fields
SMAD-INTERACTING PROTEIN-1 MOWAT-WILSON-SYNDROME EPITHELIAL-MESENCHYMAL TRANSITION HOMEODOMAIN TRANSCRIPTION FACTOR NEURAL CREST INDUCTION N-CADHERIN SWITCH TGF-BETA ZINC-FINGER STEM-CELLS HIRSCHSPRUNG-DISEASE
Zinc finger E-box binding homeobox (Zeb) 2 is a transcription factor, identified due its ability to bind Smad proteins, and consists of multiple functional domains which interact with a variety of transcriptional co-effectors. The complex nature of the Zeb2, both at its genetic and protein levels, underlie its multifunctional properties, with Zeb2 capable of acting individually or as part of a transcriptional complex to repress, and occasionally activate, target gene expression. This review introduces Zeb2 as an essential regulator of nervous system development. Zeb2 is expressed in the nervous system throughout its development, indicating its importance in neurogenic and gliogenic processes. Indeed, mutation of Zeb2 has dramatic neurological consequences both in animal models, and in humans with Mowat-Wilson syndrome, which results from heterozygous ZEB2 mutations. The mechanisms by which Zeb2 regulates the induction of the neuroectoderm (CNS primordium) and the neural crest (PNS primordium) are reviewed herein. We then describe how Zeb2 acts to direct the formation, delamination, migration and specification of neural crest cells. Zeb2 regulation of the development of a number of cerebral regions, including the neocortex and hippocampus, are then described. The diverse molecular mechanisms mediating Zeb2-directed development of various neuronal and glial populations are reviewed. The role of Zeb2 in spinal cord and enteric nervous system development is outlined, while its essential function in CNS myelination is also described. Finally, this review discusses how the neurodevelopmental defects of Zeb2 mutant mice delineate the developmental dysfunctions underpinning the multiple neurological defects observed in Mowat-Wilson syndrome patients. (C) 2015 Elsevier Ltd. All rights reserved.
OXFORD
PERGAMON-ELSEVIER SCIENCE LTD
0301-0082
81
95
10.1016/j.pneurobio.2015.07.001
Grant Details