First Author | Yang YJ | Year | 2012 |
Journal | Cell | Volume | 151 |
Issue | 5 | Pages | 1097-112 |
PubMed ID | 23178126 | Mgi Jnum | J:193339 |
Mgi Id | MGI:5468205 | Doi | 10.1016/j.cell.2012.10.043 |
Citation | Yang YJ, et al. (2012) Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. Cell 151(5):1097-112 |
abstractText | Microcephaly is a neurodevelopmental disorder causing significantly reduced cerebral cortex size. Many known microcephaly gene products localize to centrosomes, regulating cell fate and proliferation. Here, we identify and characterize a nuclear zinc finger protein, ZNF335/NIF-1, as a causative gene for severe microcephaly, small somatic size, and neonatal death. Znf335 null mice are embryonically lethal, and conditional knockout leads to severely reduced cortical size. RNA-interference and postmortem human studies show that ZNF335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. ZNF335 is a component of a vertebrate-specific, trithorax H3K4-methylation complex, directly regulating REST/NRSF, a master regulator of neural gene expression and cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF and provide the first direct genetic evidence that this pathway regulates human neurogenesis and neuronal differentiation. |