Doublecortin-Like Is Implicated in Adult Hippocampal Neurogenesis and in Motivational Aspects to Escape from an Aversive Environment in Male Mice

Abstract

Doublecortin-like (DCL) is a microtubule-associated protein that is highly homologous to doublecortin and is crucially involved in embryonic neurogenesis. Here, we have investigated the in vivo role of DCL in adult hippocampal neurogenesis by generating transgenic mice producing inducible shRNA molecules that specifically target DCL but no other splice-variants produced by the DCLK gene. DCL knockdown resulted in a significant increase in the number of proliferating BrdU + cells in the subgranular zone one day after BrdU administration. However, the number of surviving newborn adult NeuN+/BrdU + neurons are significantly decreased when inspected 4 weeks after BrdU administration suggesting a blockade of neuronal differentiation after DCL-KD. In line with this, we observed an increase in the number of proliferating cells, but a significant decrease in post mitotic DCX+ cells that are characterized by long dendrites spanning all dentate gyrus layers. Behavioural analysis showed that DCL-KD strongly extended the escape latency of mice on the circular hole board but did not affect other aspects of this behavioural task. Together, our results indicate a function for DCL in adult neurogenesis and in the motivation to escape from an aversive environment. In contrast to DCX, its pivotal role in the maturation of post-mitotic neuronal progenitor cells marks DCL as a genuine adult neurogenesis indicator in the hippocampus. 2 Significant statement Both the doublecortin and the doublecortin-like kinase (DCLK) 1 gene are crucial for embryonic neurogenesis. The genomic organization of the DCLK I gene is complex with 20 exons that produces multiple splice variants that are derived from two independent promoters. Whether or not the DCLK1 gene and, if so, which splice variant is involved in adult neurogenesis in the hippocampus is presently unknown. We have investigated specifically the role of one DCLK1 splice-variant, doublecortin-like (DCL) that shares a high level of homology with doublecortin in both sequence identity and length, in hippocampal neurogenesis. Our data indicate a pivotal role for DCL in adult hippocampus neurogenesis, which is associated with a change in hippocampal memory performance.

CircRNA FUT10 regulates the regenerative potential of aged skeletal muscle stem cells by targeting HOXA9

“…Our results suggest that miR-365a-3p can be negatively regulated by circRNA FUT10. Similarly, this argument was validated by some researches [ 35 – 37 ].…”

Singular Adult Neural Stem Cells Do Not Exist

“…In a comparative study of ovine, mouse, and human hypothalamus, Battalier et al, observed immature doublecortin (DCX)-positive and mature, Human Neuronal Protein C and D (HuC/D)-positive neurons occurring in hypothalamic nuclei [ 5 ]. This neurogenic potential of tanycytes in adult mice is further supported by their expression of the neurogenesis related protein doublecortin-like (DCL) [ 13 ], which was shown to co-localize with DCX in the mouse SVZ and SGZ [ 13 , 14 ]. In addition to rodents, SVZ and SGZ neurogenic niches have been confirmed in most mammalian species [ 15 , 16 ].…”

Many Voices in a Choir: Tumor-Induced Neurogenesis and Neuronal Driven Alternative Splicing Sound Like Suspects in Tumor Growth and Dissemination

“…It is vital for correct embryonic neurogenesis. The DCLK gene is alternately spliced to give rise to at least three isoforms ( Figure 3 ) [ 127 ]. The short isoform of DCLK lacks both doublecortin domains, implying that it cannot interact with the cytoskeleton.…”