Transcription factor AP-2 essential for cranial closure and craniofacial development

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Transcription factor AP-2 is expressed in ectoderm and neural crest cells during mouse neural tube closure.
• Cranial neural crest cells are vital for craniofacial development, skull bone formation, and cranial ganglia development.

Purpose of the Study:

• To investigate the role of the AP-2 gene during mouse embryogenesis through targeted mutagenesis.
• To understand the consequences of AP-2 gene disruption on embryonic development.

Main Methods:

• Targeted mutagenesis of the AP-2 gene in mice.
• Phenotypic analysis of AP-2 knockout (AP-2-/-) mice.

Main Results:

• AP-2 knockout mice exhibited perinatal lethality with cranio-abdominoschisis.
• Severe craniofacial, skull, sensory organ, and cranial ganglia malformations were observed.
• Failure of cranial closure occurred between 9 and 9.5 days postcoitum, associated with increased apoptosis in specific brain regions and first branchial arch mesenchyme.
• Expression of twist and Pax-3 remained unaffected.

Conclusions:

• The AP-2 gene is essential for normal mouse embryogenesis, particularly for craniofacial and neural development.
• AP-2 plays a critical role in cranial neural tube closure and preventing apoptosis during embryonic development.
• The observed defects are not due to altered expression of twist or Pax-3.