Nuclear receptor TLX (homologue of the Drosophila tailless gene) also known asNR2E1 (Nuclear receptor subfamily 2 group E member 1) is aprotein that in humans is encoded by theNR2E1gene.[5] TLX is a member of thenuclear receptor family ofintracellulartranscription factors.
TLX regulates the expression of another nuclear receptor,RAR.[6]
TLX also is essential for normal brain-eye coordination and appears to play a role in control of aggressive behavior.[7]
Adult neural stem cells are nuclear receptor TLX-positive and TLX expression in these cells is crucial in maintaining their undifferentiated state.[8] Furthermore, TLX regulates adultneural stem cell proliferation. Removal of TLX from the adultmouse brain resulted in a reduction of stem cell proliferation and spatial learning.[9]
Tlx-positive cells of thesubventricular zone of adult mouse brain are self-renewing stem cells. Mutation of the Tlx gene in adult mouse brain leads to complete loss ofneurogenesis in the subventricular zone. Tlx is also required for transition fromradial glial cells toastrocyte-like neural stem cells.[10]
TLX belongs to a small family of NRs that lack two helices in the ligand-binding domain, forming an enlarged binding pocket. Three compounds, termed ccrp1–3 (famprofazone, 1-(1,5-dimethylpyrazole-3-carbonyl)-4-(diphenylmethyl)piperazine,dydrogesterone), have been discovered in high-throughput screening that enhance TLX's ability of transcription repression with high potency.[11]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Jackson A, Panayiotidis P, Foroni L (May 1998). "The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21".Genomics.50 (1):34–43.doi:10.1006/geno.1998.5270.PMID9628820.
