Developmental Regulation of Neuregulin1 Isoforms and erbB Receptor Expression in Intact Rat Dorsal Root Ganglia

Abstract

Neuregulins (NRGs) are a family of growth factors which bind to the erbB family of tyrosine kinase receptors. The exact nature and interaction of specific NRG isoforms and erbB receptors that occur during the development of the nervous system have not been reported. In order to better understand the role that different NRG isoforms and erbB receptors play in the differentiation, proliferation, and survival of neurons and glial cells, we isolated protein and mRNA from dorsal root ganglia of rat pups between embryonic day (E) 13 and postnatal day (P) 15. The relative expression levels of the NRGs and erbB receptors for the different time points were compared using both Western and RT-PCR analyses. NRG1-type1alpha protein levels were highest at E-13 and then decreased by approximately 40% and remained constant through P-15. In contrast, mRNA levels for NRG1-type1alpha remained constant from E-15 to P-15. The protein levels for NRG1-type 1beta were similar to NRG1-type1alpha at E-13 with an approximate 40% increase in the levels at E-15 and E-17 followed by a decrease to E-13 levels for the remainder of the developmental time periods. The mRNA levels for NRG1-type1beta remained constant from E-15 to P-15. The protein and mRNA expression patterns for each erbB receptor were distinctive. The protein levels for erbB-2 were highest at E-19 while erbB-3 levels were highest at E-17 and E-18. ErbB-4 protein levels were highest at E-13 and decreased through P-15. The developmental pattern for erbB-2 and erbB-4 mRNA levels had no relation to that of the corresponding protein levels while the mRNA levels for erbB-3 were highest at E-17 and E-18 similar to the pattern observed for the erbB-3 protein levels. We concluded that both NRG and erbB expression in dorsal root ganglia are mostly translationally controlled and that NRG1 isoforms and their erbB receptors are not coordinately regulated.

Neuregulin-1β Prevents Ca2+ Overloading and Apoptosis Through PI3K/Akt Activation in Cultured Dorsal Root Ganglion Neurons with Excitotoxicity Induced by Glutamate

“…It has been determined that the protein levels of NRG-1b and its erbB receptors were constant at the higher levels around E15 (Reinhard et al 2009). In this study, DRG was dissected out from rat pups at E15.…”

“…NRG-1 is essential for myelination in the peripheral nervous system (Brinkmann et al 2008). NRG plays an important role on the genesis and differentiation of neurons in the dorsal root ganglion (DRG) (Hapner et al 2006;Reinhard et al 2009). It has been suggested that multiple NRG-1 isoforms and NRG-1 receptor subunits erbB2, erbB3, and erbB4 are expressed in rat DRG neurons (Pearson and Carroll 2004;Zhang et al 2006;Reinhard et al 2009).…”

“…NRG plays an important role on the genesis and differentiation of neurons in the dorsal root ganglion (DRG) (Hapner et al 2006;Reinhard et al 2009). It has been suggested that multiple NRG-1 isoforms and NRG-1 receptor subunits erbB2, erbB3, and erbB4 are expressed in rat DRG neurons (Pearson and Carroll 2004;Zhang et al 2006;Reinhard et al 2009). Blockade of the endogenous NRG activity of nascent neurons in the DRG completely blocks the cholinergic neurotrophic factor-induced proliferation and reduces the neurotrophin-3-mediated proliferation suggesting important role of NRG on the genesis and differentiation of neurons in the DRG (Hapner et al 2006).…”

Morphological and biomolecular characterization of the neonatal olfactory bulb ensheathing cell line

“…NRG1 is expressed not only by axons but also by astrocytes, Schwann cells and oligodendrocytes (Raabe et al, 1997) and particularly NRG ␤ isoform seems to be involved in Schwann cell proliferation and Schwann cell precursor survival (Reinhard et al, 2008). Among the different NRG1 ␤ isoforms, recently much attention has been paid to NRG1-typeIII-␤3, that elicit its biological activity on both proliferation of SC precursors and myelination (Nave and Salzer, 2006;Taveggia et al, 2005).…”

Neuregulin1 administration increases axonal elongation in dissociated primary sensory neuron cultures

“…Also ErbB2 plays a role in NRG1/ErbB transduction pathway since it functions as a co-receptor for ErbB3 and ErbB4 [24,25]. In peripheral nervous system, data on the expression of ErbB2, ErbB3 and NRG1 in both SCs and dorsal root ganglia (DRG) neurons have been reported [21,26,27]. In addition, the modulation of the NRG1/ErbB system has been demonstrated during the early stages of nerve regeneration after both severe nerve injuries characterized by substance loss [12,14,28] and injuries where nerves continuity is reestablished by means of end-to-end or end-to-side neurorrhaphy [11].…”