Shepherd Iain T, Pietsch Jacy, Elworthy Stone, Kelsh Robert N, Raible David W
Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195, USA.
Development. 2004 Jan;131(1):241-9. doi: 10.1242/dev.00912. Epub 2003 Dec 3.
Components of the zebrafish GDNF receptor complex are expressed very early in the development of enteric nervous system precursors, and are already present as these cells begin to enter the gut and migrate caudally along its length. Both gfra1a and gfra1b as well as ret are expressed at this time, while gfra2 expression, the receptor component that binds the GDNF-related ligand neurturin, is not detected until the precursors have migrated along the gut. Gfra genes are also expressed in regions of the zebrafish brain and peripheral ganglia, expression domains conserved with other species. Enteric neurons are eliminated after injection with antisense morpholino oligonucleotides against ret or against both Gfra1 orthologs, but are not affected by antisense oligonucleotides against gfra2. Blocking GDNF signaling prevents migration of enteric neuron precursors, which remain positioned at the anterior end of the gut. Phenotypes induced by injection of antisense morpholinos against both Gfra orthologs can be rescued by introduction of mRNA for gfra1a or for gfra2, suggesting that GFRalpha1 and GFRalpha2 are functionally equivalent.
斑马鱼胶质细胞系源性神经营养因子（GDNF）受体复合物的组分在肠神经系统前体发育的早期就有表达，并且在这些细胞开始进入肠道并沿其长度向尾侧迁移时就已存在。此时gfra1a和gfra1b以及ret均有表达，而gfra2（结合GDNF相关配体神经营养因子的受体组分）的表达直到前体沿着肠道迁移后才被检测到。Gfra基因也在斑马鱼脑和外周神经节区域表达，其表达域与其他物种保守。注射针对ret或针对两个Gfra1直系同源物的反义吗啉代寡核苷酸后，肠神经元会被消除，但不受针对gfra2的反义寡核苷酸的影响。阻断GDNF信号传导会阻止肠神经元前体的迁移，这些前体仍位于肠道的前端。注射针对两个Gfra直系同源物的反义吗啉代寡核苷酸所诱导的表型可通过引入gfra1a或gfra2的mRNA来挽救，这表明GFRα1和GFRα2在功能上是等效的。
