Doublecortin-like kinase 1 (DCLK1) is a Doublecortin family kinase involved in a range of brain development processes including cell migration, axon/dendrite growth, and synapse development. The Dclk1 gene potentially generates multiple splicing isoforms, but the detailed expression patterns in the brain as well as in vivo functions of each isoform are still incompletely understood. Here we assessed expression patterns of DCLK1 isoforms using multiple platforms including in silico, in situ, and in vitro datasets in the developing mouse brain, and show quantitative evidence that among the four DCLK1 isoforms, DCLK1-L and DCL are mainly expressed in the embryonic cortex whereas DCLK1-L and CPG16 become dominant compared to DCL and CARP in the postnatal cortex. We also provide compelling evidence that DCLK1 isoforms are distributed in the partially distinct brain regions in the embryonic and the postnatal stages. We further show that overexpression of DCLK1-L, but not the other isoforms, in neural progenitors causes severe migration defects in the cortex, and that the migration defects are dependent on the kinase activity of DCLK1-L. Our data thus uncover partially segregated localization of DCLK1 isoforms in the developing mouse brain and suggest different roles for distinct DCLK1 isoforms in the brain development and function.

双皮质素样激酶 1 (DCLK1) 是一种双皮质素家族激酶，参与一系列大脑发育过程，包括细胞迁移、轴突/树突生长和突触发育。Dclk1基因可能产生多种剪接异构体，但大脑中的详细表达模式以及每种异构体的体内功能仍不完全清楚。在这里，我们使用多个平台评估了 DCLK1 亚型的表达模式，包括计算机、原位和体外。发育中的小鼠大脑中的数据集，并显示定量证据表明，在四种 DCLK1 同种型中，DCLK1-L 和 DCL 主要在胚胎皮质中表达，而 DCLK1-L 和 CPG16 与出生后皮质中的 DCL 和 CARP 相比变得占主导地位。我们还提供了令人信服的证据，表明 DCLK1 亚型分布在胚胎和出生后阶段的部分不同的大脑区域。我们进一步表明，神经祖细胞中 DCLK1-L 的过表达，但不是其他同种型，会导致皮层出现严重的迁移缺陷，并且迁移缺陷取决于 DCLK1-L 的激酶活性。因此，我们的数据揭示了 DCLK1 亚型在发育中的小鼠大脑中的部分分离定位，并提出了不同 DCLK1 亚型在大脑发育和功能中的不同作用。