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Updated: Nov 10, 2025

Author Spotlight: A Pipeline to Analyze Lineage-Specific Mutant Embryos at Single-Cell Resolution
Published on: June 14, 2024
Transcriptome Regulation by Oncogenic ALK Pathway in Mammalian Cortical Development Revealed by Single-Cell RNA
Rui Mao1,2, Xiaoyun Zhang3,4, Youyong Kong5
1Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030 China.
Abstract:
Precise regulation of embryonic neurodevelopment is crucial for proper structural organization and functioning of the adult brain. The key molecular machinery orchestrating this process remains unclear. Anaplastic lymphoma kinase (ALK) is an oncogenic receptor-type protein tyrosine kinase that is specifically and transiently expressed in developing nervous system. However, its role in the mammalian brain development is unknown. We found that transient embryonic ALK inactivation caused long-lasting abnormalities in the adult mouse brain, including impaired neuronal connectivity and cognition, along with delayed neuronal migration and decreased neuronal proliferation during neurodevelopment. scRNA-seq on human cerebral organoids revealed a delayed transition of cell-type composition. Molecular characterization identified a group of differentially expressed genes (DEGs) that were temporally regulated by ALK at distinct developmental stages. In addition to oncogenes, many DEGs found by scRNA-seq are associated with neurological or neuropsychiatric disorders. Our study demonstrates a pivotal role of oncogenic ALK pathway in neurodevelopment and characterized cell-type-specific transcriptome regulated by ALK for better understanding mammalian cortical development.
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