Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development.
Neuregulins are ligands for the erbB family of receptor tyrosine kinases and mediate growth and differentiation of neural crest, muscle, breast cancer, and Schwann cells. Neuregulins contain an epidermal growth factor-like domain located C-terminally to either an Ig-like domain or a cysteine-rich domain specific to the sensory and motor neuron-derived isoform. Here it is shown that elimination of the Ig-like domain-containing neuregulins by homologous recombination results in embryonic lethality associated with a deficiency of ventricular myocardial trabeculation and impairment of cranial ganglion development. The erbB receptors are expressed in myocardial cells and presumably mediate the neuregulin signal originating from endocardial cells. The trigeminal ganglion is reduced in size and lacks projections toward the brain stem and mandible. We conclude that IgL-domain-containing neuregulins play a major role in cardiac and neuronal development.
Kramer
R
R
Department of Molecular Biology, AMGEN Center, Thousand Oaks, CA 91320-1789, USA.
Bucay
N
N
Kane
D J
DJ
Martin
L E
LE
Tarpley
J E
JE
Theill
L E
LE
D000818:Animals; D001483:Base Sequence; D003391:Cranial Nerves / Q000002:abnormalities / Q000196:embryology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005318:Fetal Heart / Q000002:abnormalities / Q000196:embryology*; D018390:Gene Targeting; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D020880:Neuregulins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D006023:Glycoproteins; D007136:Immunoglobulins; D020880:Neuregulins; D012333:RNA, Messenger