Doublecortin‐like, a microtubule‐associated protein expressed in radial glia, is crucial for neuronal precursor division and radial process stability

Abstract

During corticogenesis, progenitors divide within the ventricular zone where they rely on radial process extensions, formed by radial glial cell (RG) scaffolds, along which they migrate to the proper layers of the cerebral cortex. Although the microtubule-associated proteins doublecortin (DCX) and doublecortin-like kinase (DCLK) are critically involved in dynamic rearrangement of the cytoskeletal machinery that allow migration, little is known about their role in early corticogenesis. Here we have functionally characterized a mouse splice-variant of DCLK, doublecortin-like (DCL), exhibiting 73% amino acid sequence identity with DCX over its entire length. Unlike DCX, DCL is expressed from embryonic day 8 onwards throughout the early neuroepithelium. It is localized in mitotic cells, RGs and radial processes. DCL knockdown using siRNA in vitro induces spindle collapse in dividing neuroblastoma cells, whereas overexpression results in elongated and asymmetrical mitotic spindles. In vivo knockdown of the DCLK gene by in utero electroporation significantly reduced cell numbers in the inner proliferative zones and dramatically disrupted most radial processes. Our data emphasize the unique role of the DCLK gene in mitotic spindle integrity during early neurogenesis. In addition, they indicate crucial involvement of DCLK in RG proliferation and their radial process stability, a finding that has thus far not been attributed to DCX or DCLK.

Dynamic Expansion of Gastric Mucosal Doublecortin-Like Kinase 1–Expressing Cells in Response to Parietal Cell Loss Is Regulated by Gastrin

“…Consistent with previous studies, 25,26 YFP was detected in the nerve bundles of the submucosa and occasionally observed in the gastric mucosa (Supplemental Figure S6). However, although Dclk1 colocalized in the YFP-positive neural cells in the gastric submucosa, we did not observe any copositive cells for Dclk1 and YFP in the glands of either the gastric fundus or antrum (Figure 7).…”

“…The Dclk1 gene is expressed in precursors of neural stem cells. 25,26 Wnt1 is a crucial signaling molecule involved in neural tube formation during embryogenesis and expressed in the mid-hindbrain isthmus area and in neural crest cells. 16 Thus, we performed a lineage tracing study using the Wnt1-specific Cre driver mouse strain.…”

“…7,25 Given that the expression of Dclk1 is observed in early neurogenesis and later in the gut, we examined whether the Dclk1-expressing cells are derived from neural crest stem cells using Wnt1…”

Latent process genes for cell differentiation are common decoders of neurite extension length

“…The gene product of Metrnl is a protein akin to meteorin, a secreted protein expressed in undifferentiated neural progenitors (Nishino et al, 2004). Dclk1 encodes a microtubule-associated protein and plays a role in neurogenesis and neuronal migration (Shu et al, 2006;Vreugdenhil et al, 2007). Dlck1 has many alternative splicing variants including Carp (Ania-4) and Dclk1-short (Schenk et al, 2007;Vreugdenhil et al, 1999).…”

Functional implication of Dclk1 and Dclk1-expressing cells in cancer

“…Furthermore, multiple groups reported the importance of Dclk1 in the developing brain based on its expression in radial glia cells and neuronal precursors. [1][2][3][4][5][6][7] Outside of the nervous system, Dclk1 was initially proposed to mark quiescent gastrointestinal stem cells. 8 Careful lineage tracing studies, however, led to a more elaborate and nuanced understanding of the properties and function of Dclk1C cells in the gastrointestinal tract (see below).…”