Cretekos C J, Grunwald D J
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, 84112, USA.
Dev Biol. 1999 Jun 15;210(2):322-38. doi: 10.1006/dbio.1999.9287.
alyronz12 (aln) is a recessive lethal mutation that affects early stages of neural crest development in the zebrafish. alyron appears to be an insertional mutation as the mutation was generated following microinjection of plasmid DNA into one-cell embryos and the stably integrated transgenic sequences are closely linked to the mutation. The insertion site harbors multiple copies of the plasmid sequence that have experienced complex rearrangements. Host-insert junction fragments have been molecularly cloned and host sequences adjacent to the transgene have been used to map the mutation to the distal arm of linkage group 15. alyron function is required cell-autonomously in the neural crest lineage. alyron mutants have a severe but not complete deficit of premigratory neural crest as judged by reduced expression of several markers associated with early stages of neural crest development. Lack of premigratory neural crest is likely to account for the two most conspicuous characteristics of alyron mutants: the absence of body pigmentation and the inability to affect blood circulation. The neural crest phenotype of alyron mutants resembles that observed in mouse mutants that lack Pax-3 or both Wnt-1 and Wnt-3a function, and expression of the zebrafish homologues of these genes is greatly reduced in the dorsal neural keels of alyron mutants. In contrast, ventral neural keel identity appears unaffected. Given our findings that the mutation is unlinked to pax or wnt genes that have been described in the zebrafish, we propose that alyron is a novel gene function required for the specification and/or proliferative expansion of neural crest progenitors.
alyronz12(aln)是一种隐性致死突变,影响斑马鱼神经嵴发育的早期阶段。alyron似乎是一种插入突变,因为该突变是在将质粒DNA显微注射到单细胞胚胎后产生的,并且稳定整合的转基因序列与该突变紧密连锁。插入位点含有经历了复杂重排的质粒序列的多个拷贝。宿主-插入连接片段已被分子克隆,并且与转基因相邻的宿主序列已被用于将该突变定位到连锁群15的远端臂。alyron功能在神经嵴谱系中是细胞自主所需的。根据与神经嵴发育早期阶段相关的几种标志物表达的降低判断,alyron突变体具有严重但不完全的迁移前神经嵴缺陷。迁移前神经嵴的缺乏可能是alyron突变体两个最明显特征的原因:身体色素沉着的缺失和影响血液循环的能力缺失。alyron突变体的神经嵴表型类似于在缺乏Pax-3或Wnt-1和Wnt-3a功能的小鼠突变体中观察到的表型,并且这些基因的斑马鱼同源物的表达在alyron突变体的背侧神经嵴中大大降低。相比之下,腹侧神经嵴身份似乎未受影响。鉴于我们的发现该突变与斑马鱼中已描述的pax或wnt基因不连锁,我们提出alyron是神经嵴祖细胞的特化和/或增殖扩展所需的一种新基因功能。