J Vet Sci.  2018 Jan;19(1):21-26. 10.4142/jvs.2018.19.1.21.

Coactosin-like protein 1 inhibits neuronal migration during mouse corticogenesis

• Li G
• Yin Y
• Chen J
• Fan Y
• Ma J
• Huang Y
• Chen C
• Dai P
• Chen S
• Zhao S

• KMID: 2402691
• DOI: http://doi.org/10.4142/jvs.2018.19.1.21

Abstract

Coactosin-like protein 1 (Cotl1), a member of the actin-depolymerizing factor (ADF)/cofilin family, was first purified from a soluble fraction of Dictyostelium discoideum cells. Neuronal migration requires cytoskeletal remodeling and actin regulation. Although Cotl1 strongly binds to F-actin, the role of Cotl1 in neuronal migration remains undescribed. In this study, we revealed that Cotl1 overexpression impaired migration of both early- and late-born neurons during mouse corticogenesis. Moreover, Cotl1 overexpression delayed, rather than blocked, neuronal migration in late-born neurons. Cotl1 expression disturbed the morphology of migrating neurons, lengthening the leading processes. This study is the first to investigate the function of Cotl1, and the results indicate that Cotl1 is involved in the regulation of neuronal migration and morphogenesis.

Keyword

Cotl1 protein; actins; in utero electroporation; neuronal migration

MeSH Terms

Actins
Animals
Dictyostelium
Humans
Mice*
Morphogenesis
Neurons*
Actins

Figure

• 

  Fig. 1 RNA bioanalyzer results for coactosin-like protein 1 (Cotl1) by the polymerase chain reaction. (A) Cotl1 RNA was expressed at a low level in specific periods in developing mouse cerebral cortex. (B) Internal reference (glyceraldehyde 3-phosphate dehydrogenase [GAPDH]) expression in mouse cerebral cortex. E, embryonic days; M, marker.

• 

  Fig. 2 Coactosin-like protein 1 (Cotl1) overexpression impaired the migration of early-born neurons in a dose-dependent manner. (A) Cotl1 impeded neuronal migration at embryonic days (E)16.5. (B) Quantification of transfected neurons in each layer at E16.5. Significance of differences between the Cotl1 and green fluorescent protein (GFP) control groups for each layer were determined by using t-tests. (C) Average fluorescence intensity in intermediate zone (IZ) and cortical plate (CP) layers at E16.5 were significantly different (***p<0.001). Bars indicate mean±SEM. Scale bar = 100 µm. DAPI, 4′,6-diamidino-2-phenylindole; VZ/SVZ, ventricular zone/subventricular zone.

• 

  Fig. 3 (A) Coactosin-like protein 1 (Cotl1) overexpression slowed the migration of late-born neurons at P1. (B) Neurons reached the upper cortical plate (UCP) at P7. (C) Quantification showed that neuron numbers were significantly decreased in the CP layers in the Cotl1-transfected group than in the green fluorescent protein (GFP) control group, but were significantly increased in the intermediate zone (IZ) and ventricular zone (VZ). Scale bars = 100 µm. *p<0.05, **p<0.01, ***p<0.001. E, embryonic days; P, postnatal days; DAPI, 4′,6-diamidino-2-phenylindole; DCP, deeper cortical plate.

• 

  Fig. 4 Coactosin-like protein 1 (Cotl1) induced an abnormal morphology in neurons of the cerebral cortex. (A) The Cotl1-transfected neurons that migrated into the cortical plate were different from those in the green fluorescent protein (GFP) control group. The average length of the leading process in the Cotl1-transfected group was significantly greater than that in the GFP control group. The arrow refers to a single neuron as shown in panel B. (B) Single neuron transfected with plasmid; left image is a representative neuron from the control group and the right image is from the Cotl1-transfected group. (C) The statistic of the length of neuronal leading process. Scale bar = 10 µm. ***p<0.001. DAPI, 4′,6-diamidino-2-phenylindole.

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