Unknown,Transcriptomics,Genomics,Proteomics

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Proneurogenic ligands defined by modeling developing cortex growth factor communication networks

ABSTRACT: 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 IFNÎ³, Nrtn and glial-derived neurotrophic factor (GDNF) as ligands with unexpected roles in promoting neurogenic differentiation of NPCs in vivo. We prepared E16 cortical neuron, E13 cortical precursor and co-cultured E16 cortical neuron and E13 cortical precursor cultures from three independent biological replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Freda Miller

PROVIDER: E-GEOD-84482 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Yuzwa Scott A SA Yang Guang G Borrett Michael J MJ Clarke Geoff G Cancino Gonzalo I GI Zahr Siraj K SK Zandstra Peter W PW Kaplan David R DR Miller Freda D FD

Neuron 20160818 5

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 use ...[more]

PMID: 27545711

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Proneurogenic ligands defined by modeling developing cortex growth factor communication networks

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

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