Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development.

Kramer, Rainer; Bucay, Nathan; Kane, Darci J.; Martin, Laura E.; Tarpley, J. E.; Theill, Lars E.

doi:10.1073/pnas.93.10.4833

Cited by 206 publications

(141 citation statements)

References 33 publications

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“…ErbB-2, the most oncogenic member of the family, has no known ligand, but by decelerating ligand dissociation, it functions as a shared signaling subunit of all direct receptors (Graus-Porta et al, 1995;Karunagaran et al, 1996). Gene targeting experiments supported this notion and added more functions to the list of neuregulin roles: ErbB-2-de®cient mice (Lee et al, 1995) shared a similar phenotype with both NDF/ neuregulin-knockout animals Kramer et al, 1996), and with ErbB-4-defective mice (Gassmann et al, 1995), in that formation of the heart trabeculae was impaired, causing embryonic lethality. In addition, NDF-and ErbB-2-de®cient mice showed similar alterations in the developing nervous system; the cranial ganglia did not develop normally.…”

Section: Introductionmentioning

confidence: 98%

Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation

et al. 1997

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Two receptor tyrosine kinases, ErB-3 and ErbB-4, mediate signaling by Neu di erentiation factors (NDFs, also called neuregulins), while ErbB-1 and ErbB-2 serve as co-receptors. We show that the two NDF/neuregulin receptors di er in spatial and temporal expression patterns: The kinase-defective receptor, ErbB-3, is expressed primarily in epithelial layers of various organs, in the peripheral nervous system, and in adult brain, whereas ErbB-4 is restricted to the developing central nervous system and to the embryonic heart. An example of alternating expression of the two receptors is provided by the developing cerebellum: During postnatal cerebellar development, ErbB-4 expression slightly decreases along with a decline in NDF transcription, whereas ErbB-3 expression commences after the peak of neurogenesis. To study functional di erences, we established primary brain cultures and found that ErbB-3 was expressed only in oligodendrocytes, whereas ErbB-4 expression was shared by oligodendrocytes, astrocytes and neurons. Blocking the action of endogenous NDF in vitro, by using a soluble form of ErbB-4, accelerated neurite outgrowth in both primary cultures and in neuronal-type cultures of the P19 teratocarcinoma, suggesting an inhibitory e ect of NDF on neural di erentiation. Apparently, ErbB-3 is associated with proliferation of P19 cells, whereas ErbB-4 correlates with a di erentiated phenotype. We conclude that the two NDF receptors play distinct, rather than redundant, developmental and physiological roles.

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Section: Introductionmentioning

confidence: 98%

Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation

et al. 1997

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“…The Ig-like domain interacts with the extracellular matrix (Kramer et al, 1996a), while the cytoplasmic tail regulates the proteolytic release of the Neuregulin1 extracellular domains (Liu et al, 1998b). Therefore, these studies suggest that Ig-like Neuregulin1s and the release of membrane anchored Neuregulin1s are necessary for cardiac trabeculae formation.…”

Section: Transgenic Mouse Models With Mutations Of the Neuregulin1 Genementioning

confidence: 88%

“…EGF-like domain disruption also causes cardiac endocardial cushion defects (Meyer and Birchmeier, 1995). Hearts around E10.5 display depressed contractility, dilatation of the common ventricle, decreased emptying of the ventricle and slow irregular heart rate (Kramer et al, 1996a;Liu et al, 1998b).…”

Section: Transgenic Mouse Models With Mutations Of the Neuregulin1 Genementioning

confidence: 99%

“…(Meyer and Birchmeier, 1995) Ig-like domain (Type I and II NRG1 KO) Homozygous die around E10.5 Lack ventricular trabeculae. Heart failure (Kramer et al, 1996b) Cytoplasmic tail (Type I NRG1 KO) Homozygous die around E10.5 Lack ventricular trabeculae. Heart failure (Liu et al, 1998a) Endothelial specific conditional NRG1 KO Normal cardiac function at baseline.…”

Section: Cardiotoxicity Of Oncologic Treatments 74mentioning

confidence: 99%

“…Several transgenic mouse models are generated with deletion/disruption of the EGF-like domain, Ig-like domain or the cytoplasmic tail of the Neureuglin1 proteins (Meyer and Birchmeier, 1995;Kramer et al, 1996b;Liu et al, 1998a).…”

Section: Transgenic Mouse Models With Mutations Of the Neuregulin1 Genementioning

confidence: 99%

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Neuregulin1-ErbB Signaling in Doxorubicin-Induced Cardiotoxicity

Goukassian¹,

Morgan²,

Yan³

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Cardiotoxicity of Oncologic Treatments

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Specificity within the EGF family/ErbB receptor family signaling network

1998

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Recent years have witnessed tremendous growth in the epidermal growth factor (EGF) family of peptide growth factors and the ErbB family of tyrosine kinases, the receptors for these factors. Accompanying this growth has been an increased appreciation for the roles these molecules play in tumorigenesis and in regulating cell proliferation and differentiation during development. Consequently, a significant question has been how diverse biological responses are specified by these hormones and receptors. Here we discuss several characteristics of hormone‐receptor interactions and receptor coupling that contribute to specificity: 1) a single EGF family hormone can bind multiple receptors; 2) a single ErbB family receptor can bind multiple hormones; 3) there are three distinct functional groups of EGF family hormones; 4) EGF family hormones can activate receptors in trans, and this heterodimerization diversifies biological responses; 5) ErbB3 requires a receptor partner for signaling; and 6) ErbB family receptors differentially couple to signaling pathways and biological responses. BioEssays 20:41–48, 1998. © 1998 John Wiley & Sons, Inc.

show abstract

Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development.

Abstract: Neuregulins

Cited by 206 publications

References 33 publications

Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation

Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation

Neuregulin1-ErbB Signaling in Doxorubicin-Induced Cardiotoxicity

Specificity within the EGF family/ErbB receptor family signaling network

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