Schier A F, Neuhauss S C, Harvey M, Malicki J, Solnica-Krezel L, Stainier D Y, Zwartkruis F, Abdelilah S, Stemple D L, Rangini Z, Yang H, Driever W
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129, USA.
Development. 1996 Dec;123:165-78. doi: 10.1242/dev.123.1.165.
In a large scale mutagenesis screen for embryonic mutants in zebrafish, we have identified 63 mutations in 24 loci affecting the morphogenesis of the zebrafish brain. The expression of marker genes and the integrity of the axonal scaffold have been studied to investigate abnormalities in regionalization, neurogenesis and axonogenesis in the brain. Mutants can be broadly classified into two groups, one affecting regionalization along the anterior-posterior or dorsal-ventral axis, and the other affecting general features of brain morphology. The first group includes one locus that is required to generate the anlage of the midbrain-hindbrain boundary region at the beginning of somitogenesis. Four loci were identified that affect dorsal-ventral patterning of the brain, including the previously described cyclops locus. Mutant embryos of this class show a reduction of ventral neuroectodermal structures and variable fusion of the eyes. The second group includes a large class of mutations affecting the formation of brain ventricles. Analysis of this class reveals the requirement of a functional cardiovascular system for ventricle enlargement during embryogenesis. Mutations in one locus lead to the formation of supernumerary primary neurons, a phenotype reminiscent of neurogenic mutants in Drosophila. Other mutant phenotypes described here range from abnormalities in the fasciculation and outgrowth of axons to defects in the diameter of the neural tube. The identified loci establish the genetic foundation for a further analysis of the development of the zebrafish embryonic brain.
在一项针对斑马鱼胚胎突变体的大规模诱变筛选中，我们在24个基因座中鉴定出63个影响斑马鱼大脑形态发生的突变。我们研究了标记基因的表达和轴突支架的完整性，以调查大脑区域化、神经发生和轴突发生中的异常情况。突变体大致可分为两组，一组影响沿前后轴或背腹轴的区域化，另一组影响大脑形态的一般特征。第一组包括一个在体节发生开始时产生中脑-后脑边界区域原基所必需的基因座。鉴定出四个影响大脑背腹模式形成的基因座，包括先前描述的独眼巨人基因座。这类突变体胚胎显示腹侧神经外胚层结构减少以及眼睛不同程度的融合。第二组包括一大类影响脑室形成的突变。对这一类突变的分析揭示了胚胎发育过程中功能性心血管系统对脑室扩大的必要性。一个基因座中的突变导致额外初级神经元的形成，这一表型让人联想到果蝇中的神经发生突变体。这里描述的其他突变体表型范围从轴突的成束和生长异常到神经管直径缺陷。所鉴定的基因座为进一步分析斑马鱼胚胎大脑的发育奠定了遗传基础。
