Scientific Publications

Microcephaly Gene Links Trithorax and REST/NRSF to Control Neural Stem Cell Proliferation and Differentiation.

Publication TypeJournal Article
AuthorsYang, YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD, Gonzalez DM, Wang EP, Marshall-Walker CA, Barry BJ, Murn J., Tatarakis A., Mahajan MA, Samuels HH, Shi Y., Golden JA, Mahajnah M., Shenhav R., and Walsh CA
AbstractMicrocephaly 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.
Year of Publication2012
JournalCell
Volume151
Issue5
Pages1097-1112
Date Published (YYYY/MM/DD)2012/11/21
ISSN Number0092-8674
DOI10.1016/j.cell.2012.10.043
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/23178126?dopt=Abstract