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Distinct function of P63 isoforms during embryonic skeletal development.

Yaojuan Lu1, Sam Abbassi, Feifei Li

  • 1Department of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL 60612, USA.

Gene
|March 14, 2013
PubMed
Summary
This summary is machine-generated.

The p63 (p53 family transcription factor) isoforms, TAP63α and ΔNP63α, have distinct roles in skeletal development. While ΔNP63α appears less critical, TAP63α influences endochondral ossification, affecting bone development.

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • The p63 (p53 family transcription factor) protein family has multiple isoforms with crucial roles in development and cancer.
  • Mutations in P63 are linked to skeletal abnormalities, indicating its importance in long bone development, but isoform-specific functions remain unclear.
  • Previous studies showed TAP63α positively influences embryonic skeletal development by regulating endochondral ossification.

Purpose of the Study:

  • To investigate the distinct roles of p63 isoforms, specifically TAP63α and ΔNP63α, in embryonic skeletal development and endochondral ossification.
  • To elucidate the functional differences between TAP63α and ΔNP63α during late and early stages of skeletal development.

Main Methods:

  • Generated transgenic mice expressing ΔNP63α under a hypertrophic chondrocyte-specific promoter (Col10a1).
  • Generated transgenic mice expressing ΔNP63α and TAP63α under a chondrocyte-specific promoter (Col2a1).
  • Analyzed skeletal phenotypes at embryonic (E17.5) and postnatal (P1) stages, including ossification, and performed expression profiling and immunohistochemistry for Sox9.

Main Results:

  • Transgenic mice expressing ΔNP63α under Col10a1 or Col2a1 promoters showed no skeletal abnormalities.
  • Transgenic mice expressing TAP63α under the Col2a1 promoter exhibited reduced ossification in digit and tail bones.
  • Col2a1-TAP63α transgenic mice displayed upregulated Sox9 expression, a negative regulator of endochondral ossification.

Conclusions:

  • The p63 isoforms TAP63α and ΔNP63α play distinct roles in endochondral ossification.
  • ΔNP63α has a limited role in late embryonic skeletal development compared to TAP63α.
  • TAP63α negatively regulates endochondral ossification, potentially through Sox9 modulation, during early skeletal development.