Loss of col8a1a function during zebrafish embryogenesis results in congenital vertebral malformations.
Loss of col8a1a function during zebrafish embryogenesis results in congenital vertebral malformations.
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DOI：
10.1016/j.ydbio.2013.11.028
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发表时间：
2014-02-01
影响因子：
2.7
通讯作者：
Solnica-Krezel, Lilianna
中科院分区：
文献类型：
--
作者：
Gray, Ryan S.;Wilm, Thomas P.;Smith, Jeff;Bagnat, Michel;Dale, Rodney M.;Topczewski, Jacek;Johnson, Stephen L.;Solnica-Krezel, Lilianna
先天性脊椎畸形（CVM）发生在1/1，000活产婴儿中，在许多情况下可导致脊柱畸形，如脊柱侧凸，并导致受影响个体的残疾和痛苦。许多严重形式的疾病，如脊椎肋骨发育不全，是隐性单基因性状，影响体节发生，但大多数CVM病例的病因仍不确定。在这里，我们表明，形态缺陷的脊索在斑马鱼可以产生先天性脊柱缺陷。我们表征了三个隐性斑马鱼利维坦/col 8a 1a突变等位基因（m531，vu 41，vu 105），破坏胶原蛋白VIII型α 1a（col 8a 1a），并导致胚胎脊索折叠，因此成人脊柱畸形。此外，我们提供的证据表明，在胚胎发育过程中，col 8a 1a功能的短暂丧失或药物对赖氨酰氧化酶的抑制足以在成人脊柱中产生椎体融合和脊柱侧凸。使用周期性成像的个体斑马鱼，我们相关局灶性脊索缺陷的胚胎与脊椎畸形（VM）在成人。最后，我们发现，脊索的弯曲和扭结会导致成骨细胞的异常附着，这些细胞通常局限于发育中椎体的节段性区域。我们的研究结果提供了一种新的机制，VM的形成，独立的缺陷的体节，导致异常的骨沉积畸形脊索组织的地区。
Congenital vertebral malformations (CVM) occur in 1 in 1,000 live births and in many cases can cause spinal deformities, such as scoliosis, and result in disability and distress of affected individuals. Many severe forms of the disease, such as spondylocostal dystostosis, are recessive monogenic traits affecting somitogenesis, however the etiologies of the majority of CVM cases remain undetermined. Here we demonstrate that morphological defects of the notochord in zebrafish can generate congenital-type spine defects. We characterize three recessive zebrafish leviathan/col8a1a mutant alleles (m531, vu41, vu105) that disrupt collagen type VIII alpha1a (col8a1a), and cause folding of the embryonic notochord and consequently adult vertebral column malformations. Furthermore, we provide evidence that a transient loss of col8a1a function or inhibition of Lysyl oxidases with drugs during embryogenesis was sufficient to generate vertebral fusions and scoliosis in the adult spine. Using periodic imaging of individual zebrafish, we correlate focal notochord defects of the embryo with vertebral malformations (VM) in the adult. Finally, we show that bends and kinks in the notochord can lead to aberrant apposition of osteoblasts normally confined to well-segmented areas of the developing vertebral bodies. Our results afford a novel mechanism for the formation of VM, independent of defects of somitogenesis, resulting from aberrant bone deposition at regions of misshapen notochord tissue.
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影响因子：
1.5
作者：
DeLaurier, April;Eames, B. Frank;Blanco-Sanchez, Bernardo;Peng, Gang;He, Xinjun;Swartz, Mary E.;Ullmann, Bonnie;Westerfield, Monte;Kimmel, Charles B.
通讯作者：
Kimmel, Charles B.
纤维蛋白-2在斑马鱼脊索和血管形态发生中的重要作用。
影响因子：
2.5
作者：
Gansner, John M.;Madsen, Erik C.;Mecham, Robert P.;Gitlin, Jonathan D.
通讯作者：
Gitlin, Jonathan D.
影响因子：
12.3
作者：
Bradley, Kevin M.;Elmore, J. Bradford;Smith, Jeffrey R.
通讯作者：
Smith, Jeffrey R.
影响因子：
4.6
作者：
Juelich, Doerthe;Mould, A. Paul;Holley, Scott A.
通讯作者：
Holley, Scott A.
影响因子：
4
作者：
Kagan, HM;Li, WD
通讯作者：
Li, WD