Project 1: Investigating the alteration of Choroid plexus-CSF system in neurodevelopmental disorders.
Background: The choroid plexus, a brain structure responsible for cerebrospinal fluid secretion, plays a critical role in regulating brain function. Recent studies have linked choroid plexus dysfunction to various neurodevelopmental disorders, including autism spectrum disorder (ASD), hydrocephalus, and Coffin-Siris syndrome. Notably, increased choroid plexus volume has been observed in ASD patients, and many ASD risk genes are highly enriched in this region. However, the mechanistic involvement of the choroid plexus in ASD remains poorly understood.
Objective: Our research focuses on understanding how choroid plexus functionality is altered in mouse models of ASD. Specifically, we aim to explore whether choroid plexus fate specification, maturation, and functionality are disrupted in ASD. To address this, we will employ a multi-omic approach combined with advanced fluorescence live imaging to comprehensively analyze these processes.
Project 2: Investigating cellular and molecular defects in hippocampal development in the maternal high fat diet mouse model.
Background: Fetal brain development is shaped by various internal and external factors during pregnancy. Maternal nutrition, stress, infections, and environmental toxins are among the key elements that influence optimal neural growth. Maternal diet, particularly a high-fat diet (HFD), is a significant environmental factor associated with abnormalities in fetal brain development and functionality. With modern lifestyle changes, HFD consumption has become increasingly common, often exceeding recommended fat intake levels. Maternal HFD has been associated with an increased risk of neurodevelopmental and neurodegenerative disorders in offspring. Human cohort studies report memory deficits and reduced IQ in children born to mothers who consumed a high-fat diet during pregnancy. However, the precise mechanisms by which maternal HFD disrupts the developmental choreography of the hippocampus, the learning and memory center of the brain, remain poorly understood.
Objective: Our study aims to explore how maternal HFD influences hippocampal development, focusing on critical processes such as hippocampal cell fate specification, progenitor proliferation, and synapse formation. Specifically, we seek to investigate how the fundamental steps of hippocampal development are altered spatially and temporally due to maternal HFD. To address this, we will utilize confocal imaging coupled with cell-type-specific markers, RNA sequencing, and proteomics using a HFD mouse model as our experimental system.