Cecr2 mutations causing exencephaly trigger misregulation of mesenchymal/ectodermal transcription factors

Area of Science:

• Developmental biology
• Genetics
• Molecular biology

Background:

• Neural tube defects (NTDs) are congenital abnormalities with over 200 associated mouse genes.
• Cecr2, a subunit of the CERF chromatin remodeling complex, is implicated in NTDs.

Purpose of the Study:

• To investigate the role of Cecr2 in cranial neural tube closure.
• To characterize the effects of Cecr2 loss-of-function mutations on embryonic development.

Main Methods:

• Gene-trap mutation Cecr2(Gt45Bic) was used to study gene expression changes via microarray.
• A novel Cecr2 null allele (Cecr2(tm1.1Hemc)) was generated to assess phenotypic consequences.
• Quantitative real-time PCR (qRT-PCR) was employed to validate gene expression alterations.

Main Results:

• Cecr2(Gt45Bic) mutation led to 74% exencephaly in BALB/c mice.
• Microarray analysis identified numerous differentially expressed genes during cranial neural tube closure.
• The Cecr2 null allele exhibited stronger exencephaly and additional defects, including facial clefts and encephalocele.
• Downregulation of transcription factors Alx1/Cart1, Dlx5, Eya1, and Six1 was confirmed in Cecr2 null mutants.

Conclusions:

• Altered expression of mesenchymal/ectodermal transcription factors, such as Alx1/Cart1 and Dlx5, may underlie the NTDs observed in Cecr2-deficient embryos.
• Cecr2 plays a critical role in mammalian neural tube development.