DCX knockout ferret reveals a neurogenic mechanism in cortical development
Wei Wang,
Chonghai Yin,
Shaonan Wen,
Zeyuan Liu,
Bosong Wang,
Bo Zeng,
Le Sun,
Xin Zhou,
Suijuan Zhong,
Junjing Zhang,
Wenji Ma,
Qian Wu,
Xiaoqun Wang
Affiliations
Wei Wang
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
Chonghai Yin
Changping Laboratory, Beijing 102206, China
Shaonan Wen
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China
Zeyuan Liu
Changping Laboratory, Beijing 102206, China
Bosong Wang
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China
Bo Zeng
Changping Laboratory, Beijing 102206, China
Le Sun
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100069, China
Xin Zhou
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China; Changping Laboratory, Beijing 102206, China
Suijuan Zhong
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China; Changping Laboratory, Beijing 102206, China
Junjing Zhang
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China
Wenji Ma
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
Qian Wu
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China; Changping Laboratory, Beijing 102206, China
Xiaoqun Wang
State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, Beijing Normal University, New Cornerstone Science Laboratory, Beijing 100875, China; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Corresponding author
Summary: Lissencephaly is a rare brain malformation for which our understanding remains limited due to the absence of suitable animal models that accurately represent human phenotypes. Here, we establish doublecortin (DCX) knockout ferrets as a model that faithfully replicates key features of the disorder. We reveal the critical roles of DCX in neural progenitor cell proliferation and radial glial fiber extension, processes essential for normal cortical development. Utilizing single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics, we provide a detailed atlas of the lissencephalic cortex, illustrating disrupted neuronal lamination and the specific interactions between inhibitory and excitatory neurons. These findings enhance our understanding of the cellular and molecular mechanisms underlying lissencephaly and highlight the potential of DCX knockout ferrets as a valuable tool for neurodevelopmental research, offering insights into both the pathology of lissencephaly and the general principles of brain development.
