Bon Seong Goo¹, Dong Jin Mun¹, Seunghyun Kim¹, Truong Thi My Nhung¹, Su Been Lee ¹, Youngsik Woo ¹, Soo Jeong Kim¹, Bo Kyoung Suh¹, Sung Jin Park^1,4, Hee-Eun Lee ¹, Kunyou Park¹, Hyunsoo Jang², Jong-Cheol Rah³, Ki-Jun Yoon ², Seung Tae Baek ¹, Seung-Yeol Park ¹ and Sang Ki Park ¹

¹Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea. 
²Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea. 
³Korea Brain Research Institute, Daegu 41062, Republic of Korea. 
⁴Present address: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA. 

Corresponding authors: Correspondence to Seung-Yeol Park or Sang Ki Park.

Although large-scale genome-wide association studies (GWAS) have identified an association between MAD1L1 (Mitotic Arrest Deficient-1 Like 1) and the pathology of schizophrenia, the molecular mechanisms underlying this association remain unclear. In the present study, we aimed to address these mechanisms by examining the role of MAD1 (the gene product of MAD1L1) in key neurodevelopmental processes in mice and human organoids. Our findings indicated that MAD1 is highly expressed during active cortical development and that MAD1 deficiency leads to impairments in neuronal migration and neurite outgrowth. We also observed that MAD1 is localized to the Golgi apparatus and regulates vesicular trafficking from the Golgi apparatus to the plasma membrane, which is required for the growth and polarity of migrating neurons. In this process, MAD1 physically interacts and collaborates with the kinesin-like protein KIFC3 (kinesin family member C3) to regulate the morphology of the Golgi apparatus and neuronal polarity, thereby ensuring proper neuronal migration and differentiation. Consequently, our findings indicate that MAD1 is an essential regulator of neuronal development and that alterations in MAD1 may underlie schizophrenia pathobiology.