Dataset Information

Loss of NAC1 expression is associated with defective bony patterning in the murine vertebral axis.

ABSTRACT: NAC1 encoded by NACC1 is a member of the BTB/POZ family of proteins and participates in several pathobiological processes. However, its function during tissue development has not been elucidated. In this study, we compared homozygous null mutant Nacc1(-/-) and wild type Nacc1(+/+) mice to determine the consequences of diminished NAC1 expression. The most remarkable change in Nacc1(-/-) mice was a vertebral patterning defect in which most knockout animals exhibited a morphological transformation of the sixth lumbar vertebra (L6) into a sacral identity; thus, the total number of pre-sacral vertebrae was decreased by one (to 25) in Nacc1(-/-) mice. Heterozygous Nacc1(+/-) mice had an increased tendency to adopt an intermediate phenotype in which L6 underwent partial sacralization. Nacc1(-/-) mice also exhibited non-closure of the dorsal aspects of thoracic vertebrae T10-T12. Chondrocytes from Nacc1(+/+) mice expressed abundant NAC1 while Nacc1(-/-) chondrocytes had undetectable levels. Loss of NAC1 in Nacc1(-/-) mice was associated with significantly reduced chondrocyte migratory potential as well as decreased expression of matrilin-3 and matrilin-4, two cartilage-associated extracellular matrix proteins with roles in the development and homeostasis of cartilage and bone. These data suggest that NAC1 participates in the motility and differentiation of developing chondrocytes and cartilaginous tissues, and its expression is necessary to maintain normal axial patterning of murine skeleton.

SUBMITTER: Yap KL

PROVIDER: S-EPMC3724875 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Loss of NAC1 expression is associated with defective bony patterning in the murine vertebral axis.

Yap Kai Lee KL Sysa-Shah Polina P Bolon Brad B Wu Ren-Chin RC Gao Min M Herlinger Alice L AL Wang Fengying F Faiola Francesco F Huso David D Gabrielson Kathleen K Wang Tian-Li TL Wang Jianlong J Shih Ie-Ming IeM

PloS one 20130726 7

NAC1 encoded by NACC1 is a member of the BTB/POZ family of proteins and participates in several pathobiological processes. However, its function during tissue development has not been elucidated. In this study, we compared homozygous null mutant Nacc1(-/-) and wild type Nacc1(+/+) mice to determine the consequences of diminished NAC1 expression. The most remarkable change in Nacc1(-/-) mice was a vertebral patterning defect in which most knockout animals exhibited a morphological transformation ...[more]

PMID: 23922682

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Project description:Fishes have repeatedly evolved characteristic body shapes depending on how close they live to the substrate. Pelagic fishes live in open water and typically have narrow, streamlined body shapes; benthic and demersal fishes live close to the substrate; and demersal fishes often have deeper bodies. These shape differences are often associated with behavioral differences: pelagic fishes swim nearly constantly, demersal fishes tend to maneuver near the substrate, and benthic fishes often lie in wait on the substrate. We hypothesized that these morphological and behavioral differences would be reflected in the mechanical properties of the body, and specifically in vertebral column stiffness, because it is an attachment point for the locomotor musculature and a central axis for body bending. The vertebrae of bony fishes are composed of two cones connected by a foramen, which is filled by the notochord. Since the notochord is more flexible than bony vertebral centra, we predicted that pelagic fishes would have narrower foramina or shallower cones, leading to less notochordal material and a stiffer vertebral column which might support continuous swimming. In contrast, we predicted that benthic and demersal fishes would have more notochordal material, making the vertebral column more flexible for diverse behaviors in these species. We therefore examined vertebral morphology in 79 species using micro-computed tomography scans. Six vertebral features were measured including notochordal foramen diameter, centrum body length, and the cone angles and diameters for the anterior and posterior vertebral cones, along with body fineness. Using phylogenetic generalized least squares analyses, we found that benthic and pelagic species differed significantly, with larger foramina, shorter centra, and larger cones in benthic species. Thus, morphological differences in the internal shape of the vertebrae of fishes are consistent with a stiffer vertebral column in pelagic fishes and with a more flexible vertebral column in benthic species.

Dataset Information

Loss of NAC1 expression is associated with defective bony patterning in the murine vertebral axis.

Publications

Loss of NAC1 expression is associated with defective bony patterning in the murine vertebral axis.

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