Role of p63 in Craniofacial Muscles Development

Abstract

Background The transcription factor p63 gene is part of the p53 family of tumor suppressor genes. P63 is involved in many developmental processes including proliferation, apoptosis, differentiation, cell survival and in maintenance and stratification of epithelial tissues throughout the body. P63-/- mice show a characteristic phenotype with craniofacial malformations, absence of limbs, and epithelial defects. Previous studies have not mentioned head muscle abnormalities. However, we found that p63-/- mice have craniofacial muscle defects. Therefore, we aimed to describe the head muscle development in p63-/- mice and develop hypotheses regarding underlying mechanisms leading to the abnormalities. Methods We dissected E16 to P0 WT (wild-type) and p63-/- mice under a stereomicroscope with camera. A literature search was done to learn about processes that influence the muscle development. Results In p63-/- mice, many craniofacial muscles are thinner (e.g., masseter), without or with changes of their attachments (e.g., cleidotrapezius), or absent (e.g., tensor veli palatini). In WT mice, the levator veli palatini originates from the temporal bone (petrous part) and the tympanic tube cartilage and inserts onto the soft palate. In p63-/- mice, this muscle is thinner and at the insertion indistinguishable from the soft palate. The nasolabialis muscle originates in WT mice from the maxilla (frontal process) and inserts onto the mystacial pad (MP) surrounding vibrissae of the nasal region. In p63-/- mice, vibrissae are absent, nasal cartilage development is delayed, and the insertion of nasolabials extends over the dorsum of the nose. Discussion Some changes are best explained by the ‘nearest neighbor’ hypothesis, i.e., muscles develop towards their attachments and if the attachment is not developed then the muscles will attach on whatever is nearby. For example, in p63-/- mice, the nasolabialis that would attach onto the MP attaches to the dorsum of the nose, because the delayed development of the nasal cartilages which are overlying the MP. The compaction and proliferation of the core of branchial arches, comprised of mesodermal and neural crest cells (NCCs), is regulated by signals from epithelia. If defective epithelia are influencing proliferation of core cells, then late developing muscles might not receive enough material to differentiate (e.g., tensor veli palatini) and earlier muscles might be thinner due to less muscle cells (mesoderm-derived) and / or less connective tissue (NCC-derived). Outlook We will dissect younger p63-/- mice and examine gene expression pattern to test our hypothesis regarding compaction and proliferation in the branchial arch cores. This will result in a detailed description of head muscle development in p63-/- mice and a deepened understanding of tissue interaction during development.