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The Journal of Neuroscience, June 10, 2009, 29(23):7404-7412; doi:10.1523/JNEUROSCI.5841-08.2009

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Development/Plasticity/Repair
ZHX2 Interacts with Ephrin-B and Regulates Neural Progenitor Maintenance in the Developing Cerebral Cortex

Chen Wu,^1,2 Runxiang Qiu,¹ Jun Wang,^1,2 Heying Zhang,¹ Kiyohito Murai,¹ and Qiang Lu¹

¹Department of Neurosciences, Beckman Research Institute of the City of Hope, and ²City of Hope Graduate School of Biological Sciences, Duarte, California 91010

Correspondence should be addressed to Qiang Lu, Department of Neurosciences, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010. Email: qlu{at}coh.org

Neural progenitor cells in the ventricular zone of the developing mammalian cerebral cortex give rise to specialized cortical cell types via consecutive rounds of proliferation and differentiation, but the mechanisms by which progenitor cell self-renewal and differentiation are regulated during cortical development are not well understood. Here, we show that zinc-finger and homeodomain protein 2 (ZHX2) is specifically expressed in neural progenitor cells during cortical neurogenesis. ZHX2 binds to the cytoplasmic domain of ephrin-B1, which is expressed in cortical neural progenitors and plays a role in neural progenitor cell maintenance. ZHX2 acts as a transcriptional repressor in cell, and its repressor activity is enhanced by coexpression of an ephrin-B1 intracellular domain. Blocking ZHX2 function in cultured neural progenitor cells or in the embryonic cortex causes neuronal differentiation, whereas overexpression of ZHX2 and an ephrin-B1 intracellular domain disrupts the normal differentiation of cortical neural progenitor cells. This study identifies ZHX2 as a novel regulator of neural progenitor cell maintenance and suggests a potential nuclear mechanism of the ephrin-B function in the cortex.

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Received Dec. 8, 2008; revised April 15, 2009; accepted May 1, 2009.

Correspondence should be addressed to Qiang Lu, Department of Neurosciences, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010. Email: qlu{at}coh.org

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