Cux2 expression regulated by Lhx2 in the upper layer neurons of the developing cortex

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• The mammalian cerebrum's laminar structure involves complex gene regulation.
• Pyramidal neurons in specific cortical layers exhibit distinct gene expression patterns.
• Cux1 and Cux2 genes are crucial for neuronal development in cortical layers II-IV, regulating dendritic branching and synapse formation.

Purpose of the Study:

• To investigate the transcriptional regulation of Cux2 gene expression in the cerebral cortex.
• To identify genetic elements controlling the specific expression of Cux2 in cortical layers II-IV.

Main Methods:

• Construction of Cux2-mCherry transgenic mice using BAC transgenesis.
• Immunohistochemistry to verify mCherry expression patterns.
• Comparative genome analysis and in vivo reporter assays to identify regulatory regions.
• Analysis of Lhx2 as a potential transcriptional activator.

Main Results:

• Cux2-mCherry transgenic mice accurately recapitulated endogenous Cux2 expression in cortical layers II-IV and the corpus callosum.
• A conserved 220 bp region was identified as critical for specific cerebral Cux2 expression.
• Lhx2 was confirmed to function as a transcriptional activator in cortical layers II-IV.

Conclusions:

• Cortical layer II-IV expression of Cux2 is likely regulated by the interaction between the Cux2 enhancer (Cux2-E1) and Lhx2.
• Dysregulation of this Cux2-Lhx2 co-regulation may be linked to neurodevelopmental disorders, including autism and schizophrenia.