Krembil Research Institute, Toronto, Ontario, Canada.
Donald K. Johnson Research Institute, Toronto, Ontario, Canada.
Int J Dev Biol. 2023;67(2):49-56. doi: 10.1387/ijdb.230052pm.
The gene KIAA0319-Like (KIAA0319L) is thought to confer susceptibility for developmental dyslexia. Dyslexia may be caused by alterations in neuronal migration, and in utero knockdown of KIAA0319L in rats indicated migration errors. However, studies carried out with KIAA0319L knockout mice did not reveal an altered neuronal migration phenotype. Gene knockout may activate compensatory mechanisms to buffer against genetic mutations during development. Here we assessed the role of KIAA0319L on migrating neurons in the chick developing tectum. Whole mount in situ hybridization was performed for KIAA0319L on embryonic day (E)3 - E5 chick embryos and in situ hybridization on sections was performed at later stages. The specificity and efficiency of engineered microRNA (miRNA) constructs targeting KIAA0319L for knocking down KIAA0319L were verified. miRNAs were electroporated into E5 chick optic tecta. Our studies demonstrate that KIAA0319L is expressed in the developing chick visual system, as well as in the otic vesicles. Knockdown of KIAA0319L in the optic tectum results in abnormal neuronal migration, strengthening the argument that KIAA0319L is involved in this developmental process.
基因 KIAA0319-Like（KIAA0319L）被认为易患发育性阅读障碍。阅读障碍可能是由神经元迁移改变引起的，并且在大鼠中进行的 KIAA0319L 宫内敲低表明存在迁移错误。然而，对 KIAA0319L 敲除小鼠进行的研究并未发现神经元迁移表型改变。基因敲除可能会激活补偿机制，以在发育过程中缓冲基因突变。在这里，我们评估了 KIAA0319L 在发育中的小鸡顶盖中迁移神经元上的作用。对胚胎期（E）3-E5 小鸡胚胎进行了 KIAA0319L 的全胚胎原位杂交，并在后期进行了切片原位杂交。针对 KIAA0319L 的工程 miRNA（miRNA）构建体的特异性和效率已被验证，可用于敲低 KIAA0319L。miRNAs 被电穿孔到 E5 小鸡视顶盖中。我们的研究表明，KIAA0319L 在发育中的小鸡视觉系统以及耳部泡囊中表达。视顶盖中 KIAA0319L 的敲低导致神经元迁移异常，这进一步证明了 KIAA0319L 参与了这一发育过程。
