p57Kip2expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium

Lazaros K. Kochilas, Jun Li, Fuzi Jin, Clayton A. Buck, Jonathan A. Epstein

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


During embryonic development the heart is required to grow in size and cell number, undergo complex morphologic alterations, and function to circulate the blood. Between embryonic d 10.5 (E10.5) and E11.5, cardiac myocytes undergo rapid cell division, resulting in doubling of cardiac mass, while metabolic requirements are increased and contraction force is enhanced. Accelerated cardiomyocyte differentiation is accompanied by a significant increase in trabeculation of ventricular myocardium. Many single gene mutations in the mouse result in a "thinned myocardium" and embryonic lethality between E10.5 and E13.5 secondary to heart failure. This is the case in theSplotchmouse in which a mutation of thePax3gene results in neural crest and cardiac defects. Nevertheless, the molecular events governing these important developmental steps remain largely unknown. Here, we describe the use of suppression subtractive hybridization to identify mRNA transcripts whose expression is enhanced during this critical period in normal hearts. These genes encode functions related to maturation of the contractile apparatus, cardiomyocyte differentiation, altered cellular metabolism, and transcriptional regulation. One of the genes that we identified, p57Kip2encodes a cyclin-dependent kinase inhibitor of the p21 family. We show that p57Kip2is normally expressed in the inner trabecular layer of the developing heart. InSplotchembryos, expression of p57Kip2is expanded to encompass the entire thickness of the myocardium. This result and further structural analysis suggests that the myocardial defect ofSplotchembryos is associated with precocious cardiomyocyte differentiation.

Original languageEnglish (US)
Pages (from-to)635-642
Number of pages8
JournalPediatric Research
Issue number5
StatePublished - Apr 1999


Dive into the research topics of 'p57Kip2expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium'. Together they form a unique fingerprint.

Cite this