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Publication : Proneurogenic Ligands Defined by Modeling Developing Cortex Growth Factor Communication Networks.

First Author  Yuzwa SA Year  2016
Journal  Neuron Volume  91
Issue  5 Pages  988-1004
PubMed ID  27545711 Mgi Jnum  J:309397
Mgi Id  MGI:6757434 Doi  10.1016/j.neuron.2016.07.037
Citation  Yuzwa SA, et al. (2016) Proneurogenic Ligands Defined by Modeling Developing Cortex Growth Factor Communication Networks. Neuron 91(5):988-1004
abstractText  The neural stem cell decision to self-renew or differentiate is tightly regulated by its microenvironment. Here, we have asked about this microenvironment, focusing on growth factors in the embryonic cortex at a time when it is largely comprised of neural precursor cells (NPCs) and newborn neurons. We show that cortical NPCs secrete factors that promote their maintenance, while cortical neurons secrete factors that promote differentiation. To define factors important for these activities, we used transcriptome profiling to identify ligands produced by NPCs and neurons, cell-surface mass spectrometry to identify receptors on these cells, and computational modeling to integrate these data. The resultant model predicts a complex growth factor environment with multiple autocrine and paracrine interactions. We tested this communication model, focusing on neurogenesis, and identified IFNgamma, Neurturin (Nrtn), and glial-derived neurotrophic factor (GDNF) as ligands with unexpected roles in promoting neurogenic differentiation of NPCs in vivo.
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