Dong Jin Mun^a, Bon Seong Goo^a, Bo Kyoung Suh^a, Ji-Ho Hong^a,1, Youngsik Woo^a, Soo Jeong Kim^a, Seunghyun Kim^a, Su Been Lee^a, Yubin Won^a, Jin Yeong Yoo^a, Eunbyul Cho^a, Eun Jin Jang^a, Truong Thi My Nhung^a, Hong Minh Triet^a, Hongyul An^b, Haeryun Lee^a, Minh Dang Nguyen^c,d,e, Seung-Yeol Park^a, Seung Tae Baek^a, and Sang Ki Park^a,2

aDepartment of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea
^bDepartment of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul 03080, Korea
^cDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
^dDepartment of Cell Biology and Anatomy, Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
eDepartment of Biochemistry and Molecular Biology, Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada

¹Present address: LG Chem Ltd, Seoul 07796, Republic of Korea.
²To whom correspondence may be addressed. : Sang Ki Park

Regulation of microtubule dynamics is required to properly control various steps of neurodevelopment. In this study, we identified granule cell antiserum-positive 14 (Gcap14) as a microtubule plus-end-tracking protein and as a regulator of microtubule dynamics during neurodevelopment. Gcap14 knockout mice exhibited impaired cortical lamination. Gcap14 deficiency resulted in defective neuronal migration. Moreover, nuclear distribution element nudE-like 1 (Ndel1), an interacting partner of Gcap14, effectively corrected the downregulation of microtubule dynamics and the defects in neuronal migration caused by Gcap14 deficiency. Finally, we found that the Gcap14-Ndel1 complex participates in the functional link between microtubule and actin filament, thereby regulating their crosstalks in the growth cones of cortical neurons. Taken together, we propose that the Gcap14-Ndel1 complex is fundamental for cytoskeletal remodeling during neurodevelopmental processes such as neuronal processes elongation and neuronal migration.