Neuregulin-1{beta} induces embryonic stem cell cardiomyogenesis via ErbB3/ErbB2 receptors

Neuregulin-1β (NRG-1β) serves multiple functions during embryonic heart development by signaling through ErbB family receptor tyrosine kinases (ErbB2, ErbB3 and ErbB4). Previous studies reported that NRG-1β induces cardiomyogenesis of mouse embryonic stem cells (mESCs) at the late stage of differentiation through ErbB4 receptor activation. Here we systematically examined NRG-1β induction of cardiac myocytes in mESCs and identified a novel time window, the early first 48 hours, for NRG-1β-based cardiomyogenesis. At this time point ErbB3, but not ErbB4, is expressed. In contrast to the later differentiation of mESCs in which NRG-1β induces cardiomyogenesis via the ErbB4 receptor, we found that knocking down ErbB3 or ErbB2 with siRNA during the early differentiation inhibited NRG-1β-induced cardiomyogenesis in mESCs. Microarray analysis of RNA expression at this early time point indicates that NRG-1β treatment in mESCs resulted in gene expression changes important to differentiation including up-regulation of components of the phosphoinositol-3 kinase (PI3K), a known mediator of NRG-1β /ErbB signaling pathway, as well as activation of cAMP Responsive Element Binding Protein(CREB). Further study demonstrated that NRG-1β induced phosphorylation of CREB is required for cardiomyogenesis of mESCs. In summary, we report a previously unrecognized role of the NRG-1β/ErbB3/CREB signaling at pre-mesoderm stage fo...

Source: BJ Cell - December 24, 2013 Category: Biochemistry Authors: J Hao, C L. Galindo, T Tran, D B. Sawyer Tags: BJ Signal Source Type: research