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Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting

Julian C Lui1, Patricia Forcinito, Maria Chang

  • 1Developmental Endocrinology Branch, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, CRC, Room 1-3330, 10 Center Dr., MSC-1103, Bethesda, MD 20892-1103, USA. luichunk@mail.nih.gov

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|April 8, 2010
PubMed

Insights

Organ growth slows and stops because early life growth triggers a gene program that reduces cell proliferation. This discovery sheds light on the mechanisms behind growth cessation in juvenile animals.

Area of Science:

  • Developmental biology
  • Molecular biology
  • Epigenetics

Background:

  • Adults cease growing, while children continue to develop.
  • Organ growth cessation results from a progressive decline in cell proliferation starting in early life.
  • The mechanisms driving this growth deceleration remain largely unknown.

Purpose of the Study:

  • To identify the gene expression programs associated with growth deceleration in juvenile rats.
  • To investigate the underlying epigenetic mechanisms and physiological drivers of this growth program.

Main Methods:

  • Expression microarray and real-time PCR were used to identify gene expression patterns in rat lung, kidney, and liver.
  • Gene ontology analyses and siRNA-mediated knockdown were employed to assess gene function.
  • A tryptophan-deficient diet was used to temporarily inhibit juvenile growth, followed by microarray analysis.

Main Results:

  • A common gene expression program was identified in multiple organs during growth deceleration in juvenile rats.
  • Many down-regulated genes in this program were found to be growth-promoting.
  • Declining histone H3K4 trimethylation with age suggested epigenetic regulation, and growth inhibition delayed the genetic program, indicating it's growth-driven, not age-driven.

Conclusions:

  • Early life growth induces a progressive down-regulation of proliferation-stimulating genes.
  • This genetic program leads to the deceleration and eventual cessation of organ growth.
  • Epigenetic mechanisms and body growth itself appear to drive this process.

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