3,773,919 A 11/1973 Boswell et al. 4,179,337 A 12/1979 Davis et al. 4,301,144 A 11/1981 Iwashita et al. 4,485,045 A 11/1984 Regen 4,496,689 A 1/1985 Mitra 4,544,545 A 10/1985 Ryan et al. 4,640,835 A 2/1987 Shimizu et al. 4,670,417 A 6/1987 Iwasaki et al. 4,791,192 A 12/1988 Nakagawa et al. 5,367,060 A 11/1994 Vandlen et al. 5,530,109 A 6/1996 Goodearl et al. 5,641,869 A 6/1997 Vandlen et al. 5,...

The Neuregulin is a member of the epidermal growth factors (EGF) family of receptor kinases, was originally identified as the product of the transforming gene derived from chemically induced rat neuroblastoms. A variety of different protein isoforms are produced from single Neuregulin gene. Four distinct vertebrate gene encode Neuregulin, prosaically named NRG1, NRG2, NRG3, and NRG4. Most of bi...

We are interested in the signaling between axons and glia that leads to myelination and maintenance of the myelin internode, and we have focused on the role of neuregulins and their receptors. Neuregulins are a family of ligands that includes heregulin, neu differentiation factor, glial growth factor, and the acetylcholine receptor-inducing activity. Three signal transducing transmembrane recep...

Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each mole...

Axonal surface proteins encompass a group of heterogeneous molecules, which exert a variety of different functions in the highly interdependent relationship between axons and Schwann cells. We recently revealed that the tumour suppressor protein merlin, mutated in the hereditary tumour syndrome neurofibromatosis type 2, impacts significantly on axon structure maintenance in the peripheral nervo...

Heart development requires cardiomyocyte proliferation, coupled with morphogenic differentiation of the inner trabecular myocardium and the outer compact zone myocardium. In mouse embryos lacking the retinoic acid receptor RXRalpha, proliferation and morphogenesis of the compact zone fails. We demonstrated previously that epicardial cells, in response to retinoic acid, secrete an activity that ...

The cardiac conduction system is a network of cells responsible for the rhythmic and coordinated excitation of the heart. Components of the murine conduction system, including the peripheral Purkinje fibers, are morphologically indistinguishable from surrounding cardiomyocytes, and a paucity of molecular markers exists to identify these cells. The murine conduction system develops in close asso...

Signaling by the epidermal growth factor (EGF) family and the neuregulin group of ligands is mediated by four ErbB receptor tyrosine kinases, that form homo- and heterodimeric complexes. Paradoxically, the neuregulin receptor ErbB-3 is devoid of catalytic activity, but its heterodimerization with other ErbBs, particularly the ligand-less ErbB-2 oncoprotein of carcinomas, reconstitutes superior ...

Smoking is currently the leading cause of preventable death in the United States and is responsible for over four million deaths annually worldwide. Therefore, there is a vast clinical unmet need with regards to therapeutics targeting smoking cessation. This is even more apparent when examining smokers co-morbid with psychiatric illness, as rates of smoking in this population are ~4× higher tha...

Programmed cell death during development resulting from the lack of appropriate survival factors has been demonstrated in both neurons and oligodendrocytes and occurs mostly in the form of apoptosis. We now demonstrate that Schwann cells in the rat sciatic nerve undergo apoptosis during early postnatal development and that the amount of apoptosis is markedly increased by axotomy. The apoptotic ...