Prep 1.1 has essential genetic functions in hindbrain development and cranial neural crest cell differentiation
Prep 1.1 has essential genetic functions in hindbrain development and cranial neural crest cell differentiation
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DOI：
10.1242/dev.00948
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发表时间：
2004-02-01
期刊：
影响因子：
4.6
通讯作者：
Argenton, F
中科院分区：
文献类型：
--
作者：
Deflorian, G;Tiso, N;Argenton, F
在这项研究中，我们分析了Meinox基因prep1.1在斑马鱼发育过程中的功能。Meinox蛋白与Hox和Pbx成员形成异源三聚体复合物，增加Hox蛋白在体外和体内的DNA结合特异性。然而，一个特定的Meinox蛋白在体内Hox活性的调节中的作用尚未得到证实。原位杂交显示prep1.1在受精后24小时内表达，并且在48小时后局限于头部。吗啉代诱导制备1.1.功能丧失导致CNS中显著的细胞凋亡。后脑分割和图案化受到严重影响，如几个后脑标记物（foxb 1.2/马里波萨，krox 20，pax 2.1和pax 6.1）的缺失或表达缺陷所揭示的，包括前部表达的Hox基因（hoxb 1a，hoxa 2和hoxb 2），面神经运动神经元的迁移受损，以及除Mauthner细胞外缺乏网状脊髓神经元（RSN）。此外，prep1.1变形的头部缺乏所有的咽软骨。这不是由于缺乏神经嵴细胞或其迁移到咽弓受损，如dlx 2和snail 1的表达所示，而是由于这些细胞不能分化成软骨细胞。我们的研究结果表明，prep1.1在颅面软骨发生中具有独特的遗传功能，并且作为Meinox-PBC-Hox三聚体的成员，它在后脑发育中起着至关重要的作用。
In this study we analysed the function of the Meinox gene prep1.1 during zebrafish development. Meinox proteins form heterotrimeric complexes with Hox and Pbx members, increasing the DNA binding specificity of Hox proteins in vitro and in vivo. However, a role for a specific Meinox protein in the regulation of Hox activity in vivo has not been demonstrated. In situ hybridization showed that prep1.1 is expressed maternally and ubiquitously up to 24 hours post-fertilization (hpf), and restricted to the head from 48 hpf onwards. Morpholino-induced prep1.1. loss-of-function caused significant apoptosis in the CNS. Hindbrain segmentation and patterning was affected severely, as revealed by either loss or defective expression of several hindbrain markers (foxb1.2/mariposa, krox20, pax2.1 and pax6.1), including anteriorly expressed Hox genes (hoxb1a, hoxa2 and hoxb2), the impaired migration of facial nerve motor neurons, and the lack of reticulospinal neurons (RSNs) except Mauthner cells. Furthermore, the heads of prep1.1 morphants lacked all pharyngeal cartilages. This was not caused by the absence of neural crest cells or their impaired migration into the pharyngeal arches, as shown by expression of dlx2 and snail1, but by the inability of these cells to differentiate into chondroblasts. Our results indicate that prep1.1 has a unique genetic function in craniofacial chondrogenesis and, acting as a member of Meinox-Pbc-Hox trimers, it plays an essential role in hindbrain development.