This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Li, W. Articles by Shi, Y. Search for Related Content PubMed PubMed Citation Articles by Li, W. Articles by Shi, Y.

Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

Neuroscience Division (W.L., G.S., S.Y., Q.Q., Y.S.), Beckman Research Institute of City of Hope, Duarte, California 91010; and Laboratory of Molecular Neuroscience (K.N.), Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0101, Japan

Address all correspondence and requests for reprints to: Yanhong Shi, Neuroscience Division, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, California 91010. E-mail: yshi{at}coh.org.

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

NURSA Molecule Pages Link:

Nuclear Receptors:   TLX