Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain

Abstract

Neural progenitor proliferation, differentiation and migration are continually active in the rostral migratory stream of the adult brain. Here, we show that the receptor tyrosine kinase ErbB4 is expressed prominently by the neuroblasts present in the subventricular zone and the rostral migratory stream. The neuregulins (NRG1-NRG3), which have been identified as ErbB4 ligands, are detected either in the stream or in adjacent regions. Mice deficient in ErbB4 expressed under the control of either the nestin or the hGFAP promoter have altered neuroblast chain organization and migration and deficits in the placement and differentiation of olfactory interneurons. These findings suggest that ErbB4 activation helps to regulate the organization of neural chains that form the rostral migratory stream and influences the differentiation of olfactory interneuronal precursors.

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

“…Receptor-ligand interaction induces the homo- or heterodimerization with other members of the ErbB receptor family, which in turn results in the activation of several intracellular signalling pathways and the induction of cellular responses including migration of neuronal precursor cells [4-6]. In vivo studies demonstrate that the NRG1/ErbB4 system is involved in tangential migration of olfactory bulb (OB) interneuron precursors in the rostral migratory stream (RMS) [7] and of cortical interneuron precursors migrating from the ventral telencephalon [8]. …”

Elevated neuregulin-1 and ErbB4 protein in the prefrontal cortex of schizophrenic patients

“…Neuregulin-1 (NRG1) and its receptor, ErbB4, have been genetically linked to schizophrenia susceptibility Nicodemus et al 2006;Norton et al 2006;Silberberg et al 2006;Stefansson et al 2002) and are critical in neurodevelopment (Anton et al 2004;Ozaki et al 2000;Sardi et al 2006). Hence, NRG1 and ErbB4 are appealing molecules to study in schizophrenia, since this disease is hypothesized to have genetic and neurodevelopmental origins (Akbarian et al 1996;Eastwood and Harrison 2003;Jones et al 1994).…”

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

“…[8][9][10][11] ERBB4 plays a critical role in the development of the brain, and has been shown to directly influence the proliferation, organization and migration of cells in the rostral migratory stream. [12][13][14] There is now emerging evidence that the gene for ERBB4 also influences risk for schizophrenia, 15,16 especially when considered together with NRG1. 16 Moreover, there is evidence from postmortem mRNA studies for alterations in the levels of ERBB4 15 (as well as the ERBB3 coreceptor [17][18][19][20][21] ) in schizophrenia.…”