Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis

Tushar J Desai1, Felicia Chen, Jining Lü

  • 1Pulmonary Center, Boston University School of Medicine, 80 East Concord Street R-304, Boston, MA 02118, USA.

Developmental Biology
|January 24, 2006
PubMed

Insights

Retinoic acid (RA) is not essential for initial lung cell fate but is crucial for proper lung bud formation. Balanced signaling through retinoic acid receptors (RAR) alpha and beta is critical for early lung development.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Retinoic acid (RA) signaling is vital for organ development, yet its role in early lung development remains unclear.
  • Understanding how different retinoic acid receptors (RARs) mediate RA effects is crucial for comprehending lung organogenesis.

Purpose of the Study:

  • To investigate the influence of RA on the initial stages of lung development.
  • To elucidate the specific roles of RAR alpha and RAR beta in mediating RA's effects on lung initiation.

Main Methods:

  • Utilized genetic (Raldh2 null mice), pharmacological (synthetic retinoids), and explant culture techniques.
  • Analyzed lung development initiation in mice lacking RA signaling from the earliest foregut stages.
  • Investigated the effects of selective RAR alpha and RAR beta activation.

Main Results:

  • RA is dispensable for lung cell fate specification in the endoderm.
  • Activation of RAR beta, but not RAR alpha, induces fibroblast growth factor Fgf10 and lung bud morphogenesis.
  • Endogenous RAR alpha activity is required for maintaining RA signaling and refining RAR beta-mediated effects.

Conclusions:

  • Balanced activation of RAR alpha and RAR beta is critical for proper lung bud initiation.
  • Specific RARs play distinct and complementary roles in early lung development and endodermal differentiation.

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