ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice.
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.
Erickson
S L
SL
Department of Molecular Biology, Genetech Inc., South San Francisco, California 94080, USA. erickson.sharon@gene.com
O'Shea
K S
KS
Ghaboosi
N
N
Loverro
L
L
Frantz
G
G
Bauer
M
M
Lu
L H
LH
Moore
M W
MW
D000311:Adrenal Glands / Q000196:embryology; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002531:Cerebellum / Q000196:embryology*; D004848:Epithelium / Q000196:embryology; D066246:ErbB Receptors / Q000502:physiology*; D005724:Ganglia / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D018398:Homeodomain Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010179:Pancreas / Q000196:embryology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D020893:Receptor, ErbB-3; D013270:Stomach / Q000196:embryology; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D066246:ErbB Receptors; D006023:Glycoproteins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C106185:engrailed homeobox proteins