ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice

Development. 1997 Dec;124(24):4999-5011. doi: 10.1242/dev.124.24.4999.


Heregulins bind directly to ErbB3 and ErbB4 receptors, leading to multiple dimerization possibilities including heterodimerization with the ErbB2 receptor. We have generated ErbB3-, ErbB2- and heregulin-deficient mice to assess their roles in development and differentiation. Heregulin(-/-) and ErbB2(-/-) embryos died on E10.5 due to a lack of cardiac ventricular myocyte differentiation; ErbB3(-/-) embryos survived until E13.5 exhibiting cardiac cushion abnormalities leading to blood reflux through defective valves. In ErbB3(-/-) embryos, the midbrain/hindbrain region was strikingly affected, with little differentiation of the cerebellar plate. Cranial ganglia defects, while present in all three nulls, were less severe in ErbB3(-/-) embryos. The cranial ganglia defects, along with a dramatic reduction in Schwann cells, enteric ganglia and adrenal chromaffin cells, suggests a generalized effect on the neural crest. Numerous organs, including the stomach and pancreas also exhibited anomalous development.

MeSH terms

  • Adrenal Glands / embryology
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation
  • Cerebellum / embryology*
  • Epithelium / embryology
  • ErbB Receptors / physiology*
  • Ganglia / embryology
  • Gene Expression Regulation, Developmental
  • Gene Targeting
  • Glycoproteins / genetics
  • Glycoproteins / physiology*
  • Heart / embryology*
  • Homeodomain Proteins / analysis
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Pancreas / embryology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • RNA, Messenger / analysis
  • Rats
  • Receptor, ErbB-2 / physiology*
  • Receptor, ErbB-3
  • Stomach / embryology
  • Transcription Factors*
  • Wnt Proteins
  • Zebrafish Proteins*


  • Glycoproteins
  • Homeodomain Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transcription Factors
  • Wnt Proteins
  • Zebrafish Proteins
  • engrailed homeobox proteins
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3