Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull
Hedgehog signaling is required for cranial neural crest morphogenesis and chondrogenesis at the midline in the zebrafish skull
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DOI：
10.1242/dev.01943
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发表时间：
2005-09-01
期刊：
影响因子：
4.6
通讯作者：
Schilling, TF
中科院分区：
文献类型：
--
作者：
Wada, N;Javidan, Y;Schilling, TF
形成脊椎动物头部骨骼的神经嵴细胞迁移并与周围组织相互作用以形成头骨，这些过程中的缺陷是许多人类颅面综合征的基础。中线信号在前脑颅的发育中起着至关重要的作用，前脑颅形成了腹侧脑颅和腭，在这里，我们探讨了Hedgehog（Hh）信号在这一过程中的作用。使用sox10：egfp转基因跟踪活胚胎中神经嵴细胞的运动，并使用活体染料标记生成命运图，我们发现不同的神经嵴群体形成了幼虫前脑颅的两个主要软骨成分：成对的小梁和中线筛骨。通过分析斑马鱼突变体破坏音刺猬（shh）的表达，我们证明，shh是指定这些元素在中线的祖细胞的运动，并诱导他们形成软骨。用环巴胺治疗，以阻止Hh信号在不同阶段，表明，虽然在形态发生的要求发生在神经嵴迁移脑下，软骨发生的要求发生后，细胞形成单独的小梁和筛窦冷凝。细胞移植表明，这些也反映了Shh的不同来源，一个来自控制小梁形态发生的腹侧神经管，一个来自促进软骨形成的口腔外胚层。我们的研究结果表明，Shh在中线神经嵴细胞的运动，以及在其分化成软骨的一个新的作用，并有助于解释为什么骨骼融合和腭裂与Hh信号的损失在holoproproencephalic人类。
Neural crest cells that form the vertebrate head skeleton migrate and interact with surrounding tissues to shape the skull, and defects in these processes underlie many human craniofacial syndromes. Signals at the midline play a crucial role in the development of the anterior neurocranium, which forms the ventral braincase and palate, and here we explore the role of Hedgehog (Hh) signaling in this process. Using sox10:egfp transgenics to follow neural crest cell movements in the living embryo, and vital dye labeling to generate a fate map, we show that distinct populations of neural crest form the two main cartilage elements of the larval anterior neurocranium: the paired trabeculae and the midline ethmoid. By analyzing zebrafish mutants that disrupt sonic hedgehog (shh) expression, we demonstrate that shh is required to specify the movements of progenitors of these elements at the midline, and to induce them to form cartilage. Treatments with cyclopamine, to block Hh signaling at different stages, suggest that although requirements in morphogenesis occur during neural crest migration beneath the brain, requirements in chondrogenesis occur later, as cells form separate trabecular and ethmoid condensations. Cell transplantations indicate that these also reflect different sources of Shh, one from the ventral neural tube that controls trabecular morphogenesis and one from the oral ectoderm that promotes chondrogenesis. Our results suggest a novel role for Shh in the movements of neural crest cells at the midline, as well as in their differentiation into cartilage, and help to explain why both skeletal fusions and palatal clefting are associated with the loss of Hh signaling in holoprosencephalic humans.