tgfβ3 regulation of chondrogenesis and osteogenesis in zebrafish is mediated through formation and survival of a subpopulation of the cranial neural crest
tgfβ3 regulation of chondrogenesis and osteogenesis in zebrafish is mediated through formation and survival of a subpopulation of the cranial neural crest
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DOI：
10.1016/j.mod.2010.04.003
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发表时间：
2010-07-01
影响因子：
2.6
通讯作者：
Chong, Samuel S.
中科院分区：
文献类型：
--
作者：
Cheah, Felicia S. H.;Winkler, Christoph;Chong, Samuel S.
斑马鱼tgf β 3在迁移的神经嵴细胞亚群、发育中的咽弓和颅神经软骨中强烈表达。为了研究tgf β 3在头部骨骼形成中的调节作用，我们敲低了斑马鱼的tgf β 3，发现颅面软骨形成受损，在选定的颅神经和咽弓软骨中的畸形是明显的。在胚胎中过度表达tgf β 3会导致颅面软骨变小而没有任何明显的畸形。这些缺陷表明tgf β 3是正常软骨形成所必需的。为了解决导致观察到的畸形的细胞机制，我们分析了morphant和tgf β 3过表达的鱼的颅神经嵴发育。我们观察到在tgf β 3基因敲低的胚胎中，迁移前和迁移前颅神经嵴减少，颅神经嵴是颅神经软骨和咽弓的前体。相反，在过度表达tgf β 3的胚胎中，只有迁移神经嵴减少。这提出了颅神经嵴细胞数量减少是细胞凋亡增加的结果的可能性。与此相一致，显着升高的TUNEL染色中脑和后脑，并在morphant中观察到发育中的咽弓区域，而TGF β 3过表达的胚胎在发育中的咽弓区域显示出轻微增加的细胞凋亡。我们认为tgf β 3的抑制和过度表达都会导致软骨细胞和骨细胞形成的减少，但程度不同，机制也不同。在tgf β 3抑制的胚胎中，这是由于颅神经嵴细胞亚群的形成和存活受损，通过显著增加含有颅神经嵴细胞的区域中的凋亡，而在v过度表达的胚胎中，较温和的表型也是由于这些区域中的凋亡轻微升高。因此，适当的颅神经嵴的形成和存活，以及最终的颅面软骨形成和骨形成，都依赖于斑马鱼中tgf β 3蛋白水平的严格调节。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Zebrafish tgf beta 3 is strongly expressed in a subpopulation of the migrating neural crest cells, developing pharyngeal arches and neurocranial cartilages. To study the regulatory role of tgf beta 3 in head skeletal formation, we knocked down tgf beta 3 in zebrafish and found impaired craniofacial chondrogenesis, evident by malformations in selected neurocranial and pharyngeal arch cartilages. Over-expressing tgf beta 3 in embryos resulted in smaller craniofacial cartilages without any gross malformations. These defects suggest that tgf beta 3 is required for normal chondrogenesis. To address the cellular mechanisms that lead to the observed malformations, we analyzed cranial neural crest development in morphant and tgf beta 3 over-expressing fish. We observed reduced pre-migratory and migratory cranial neural crest, the precursors of the neurocranial cartilage and pharyngeal arches, in tgf beta 3 knockdown embryos. In contrast, only the migratory neural crest was reduced in embryos over-expressing tgf beta 3. This raised the possibility that the reduced number of cranial neural crest cells is a result of increased apoptosis. Consistent with this, markedly elevated TUNEL staining in the midbrain and hindbrain, and developing pharyngeal arch region was observed in morphants, while tgf beta 3 over-expressing embryos showed marginally increased apoptosis in the developing pharyngeal arch region. We propose that both tgf beta 3 suppression and over-expression result in reduced chondrocyte and osteocyte formation, but to different degrees and through different mechanisms. In tgf beta 3 suppressed embryos, this is due to impaired formation and survival of a subpopulation of cranial neural crest cells through markedly increased apoptosis in regions containing the cranial neural crest cells, while in v over-expressing embryos, the milder phenotype is also due to a slightly elevated apoptosis in these regions. Therefore, proper cranial neural crest formation and survival, and ultimately craniofacial chondrogenesis and osteogenesis, are dependent on tight regulation of tgf beta 3 protein levels in zebrafish. (C) 2010 Elsevier Ireland Ltd. All rights reserved.