The role of bone morphogenetic proteins in vertebral development

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• The formation of the vertebral spinous process involves Msx1 and Msx2 gene expression in mesenchyme.
• The dorsal neural tube can induce somitic mesenchyme differentiation into subcutaneous cartilage.

Purpose of the Study:

• To investigate the role of Bone Morphogenetic Protein 4 (BMP4) in vertebral cartilage development.
• To elucidate the molecular mechanisms controlling the differentiation of ventrolateral and dorsal vertebral cartilage.

Main Methods:

• Grafting of mouse BMP4 or human BMP2-producing cells dorsally and laterally to the developing neural tube in chick embryos.
• Analysis of gene expression patterns (Bmp4, Msx1, Msx2, Pax1, Pax3) in response to BMP cell grafts.
• Histological examination of vertebral development, including cartilage differentiation and spinous process formation.

Main Results:

• Dorsal BMP-producing cell grafts increased Msx-expressing mesenchymal cells, leading to enlarged dorsal vertebrae, fusion, and 'giant' spinous process-like structures.
• Lateral BMP-producing cell grafts inhibited Pax1 and Pax3 gene expression, induced Msx gene expression, and suppressed sclerotomal cell growth and cartilage differentiation.
• BMP-producing cells induced dorsalization of the neural tube, evidenced by Msx and Pax3 gene expression in the basal plate.

Conclusions:

• Vertebral cartilage differentiation is regulated by distinct molecular mechanisms for ventrolateral and dorsal components.
• Ventrolateral cartilage development is influenced by signals from the floor plate-notochord complex, inhibiting dorsal spinous process formation.
• Dorsal spinous process formation and differentiation of dorsal subcutaneous cartilage require BMP4 signaling.