title: Nlz belongs to a family of zinc-finger-containing repressors and controls segmental gene expression in the zebrafish hindbrain.
abstract: The zebrafish nlz gene has a rostral expression limit at the presumptive rhombomere (r) 3/r4 boundary during gastrula stages, and its expression progressively expands rostrally to encompass both r3 and r2 by segmentation stages, suggesting a role for nlz in hindbrain development. We find that Nlz is a nuclear protein that associates with the corepressor Groucho, suggesting that Nlz acts to repress transcription. Consistent with a role as a repressor, misexpression of nlz causes a loss of gene expression in the rostral hindbrain, likely due to ectopic nlz acting prematurely in this domain, and this repression is accompanied by a partial expansion in the expression domains of r4-specific genes. To interfere with endogenous nlz function, we generated a form of nlz that lacks the Groucho binding site and demonstrate that this construct has a dominant negative effect. We find that interfering with endogenous Nlz function promotes the expansion of r5 and, to a lesser extent, r3 gene expression into r4, leading to a reduction in the size of r4. We conclude that Nlz is a transcriptional repressor that controls segmental gene expression in the hindbrain. Lastly, we identify additional nlz-related genes, suggesting that Nlz belongs to a family of zinc-finger proteins.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, and Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Runko
authors.forename: Charles G
authors.initials: CG
authors.lastname: Sagerström
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D051379:Mice; D010802:Phylogeny; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C091023:gro protein, Drosophila