Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development.
Zebrafish Zic2a and Zic2b regulate neural crest and craniofacial development.
复制标题
DOI：
10.1016/j.ydbio.2013.04.033
复制
发表时间：
2013-08-01
影响因子：
2.7
通讯作者：
Grinblat, Yevgenya
中科院分区：
文献类型：
--
作者：
TeSlaa, Jessica J.;Keller, Abigail N.;Nyholm, Molly K.;Grinblat, Yevgenya
前脑无裂畸形（HPE）是人类前脑最常见的畸形，与颅面骨骼的缺陷有关。ZIC2是一种锌指转录因子，与HPE和人类一组特征性的畸形面部特征密切相关。我们以前已经确定了斑马鱼Zic 2在前脑发育中的重要功能。在这里，我们证明了ZIC2的直系同源物zic2a和zic2b也调节形成斑马鱼颅面骨骼，包括颌骨和颅神经软骨，并使用斑马鱼研究Zic2调节的过程，可能有助于HPE的复杂病因。使用时间控制Zic2a过表达，我们表明，发展中的颅面软骨是敏感的Zic2海拔前24 hpf。这种敏感性窗口与神经嵴（NC）细胞的临界扩张和迁移重叠，神经嵴细胞从发育中的神经管迁移到脊椎动物颅面结构。我们表明，zic2b影响NC的诱导在神经板边界，而zic2a和zic2b调节NC迁移开始，并强烈有助于色素细胞的发展。Zic2耗竭和早期异位Zic2表达在24hpf引起NC衍生的颌前体的中度、不完全的渗透性错误图案化，然而到2dpf，Zic2表达的这些变化导致深度错误图案化的软骨形成凝聚。我们将这种差异归因于Zic2a和Zic2b在形成前脑原基中的额外作用，前脑原基是颅面发育过程中的重要信号源。这一假设得到了以下证据的支持：移植的Zic 2缺陷细胞可以在野生型背景下促进颅面软骨。总的来说，这些数据表明，斑马鱼Zic 2在颅面发育过程中起着双重作用，有助于颅面形态发生的两个不同方面：（1）神经嵴诱导和迁移，以及（2）颅面软骨形成凝聚附近组织的早期模式。
Holoprosencephaly (HPE), the most common malformation of the human forebrain, is associated with defects of the craniofacial skeleton. ZIC2, a zinc-finger transcription factor, is strongly linked to HPE and to a characteristic set of dysmorphic facial features in humans. We have previously identified important functions for zebrafish Zic2 in the developing forebrain. Here, we demonstrate that ZIC2 orthologs zic2a and zic2b also regulate the forming zebrafish craniofacial skeleton, including the jaw and neurocranial cartilages, and use the zebrafish to study Zic2-regulated processes that may contribute to the complex etiology of HPE. Using temporally controlled Zic2a overexpression, we show that the developing craniofacial cartilages are sensitive to Zic2 elevation prior to 24hpf. This window of sensitivity overlaps the critical expansion and migration of the neural crest (NC) cells, which migrate from the developing neural tube to populate vertebrate craniofacial structures. We demonstrate that zic2b influences the induction of NC at the neural plate border, while both zic2a and zic2b regulate NC migratory onset and strongly contribute to chromatophore development. Both Zic2 depletion and early ectopic Zic2 expression cause moderate, incompletely penetrant mispatterning of the NC-derived jaw precursors at 24hpf, yet by 2dpf these changes in Zic2 expression result in profoundly mispatterned chondrogenic condensations. We attribute this discrepancy to an additional role for Zic2a and Zic2b in patterning the forebrain primordium, an important signaling source during craniofacial development. This hypothesis is supported by evidence that transplanted Zic2-deficient cells can contribute to craniofacial cartilages in a wild-type background. Collectively, these data suggest that zebrafish Zic2 plays a dual role during craniofacial development, contributing to two disparate aspects of craniofacial morphogenesis: (1) Neural crest induction and migration, and (2) early patterning of tissues adjacent to craniofacial chondrogenic condensations.
登录
查看更多内容
影响因子：
4.6
作者：
Blank, Marissa C.;Grinberg, Inessa;Millen, Kathleen J.
通讯作者：
Millen, Kathleen J.
影响因子：
4.6
作者：
Barrallo-Gimeno, A;Holzschuh, J;Knapik, EW
通讯作者：
Knapik, EW
影响因子：
64.8
作者：
Brewster, R;Lee, J;Altaba, ARI
通讯作者：
Altaba, ARI
影响因子：
2.5
作者：
Cresko, WA;Yan, YL;Postlethwait, JH
通讯作者：
Postlethwait, JH
影响因子：
4.6
作者：
Burstyn-Cohen, T;Stanleigh, J;Kalcheim, C
通讯作者：
Kalcheim, C