Control of neural crest multipotency by Wnt signaling and the Lin28/let-7 axis

• DOI: 10.7554/elife.40556
• Publication Date: 2018-12-06T13:04:52Z
• Authors: Debadrita Bhattac...; Megan Rothstein; Ana Paula Azambuja; Marcos Simoes-Costa
• Keywords: Lin28; 0301 basic medicine; Transcription, Genetic; QH301-705.5; Wnt singling; Science; Chick Embryo; Morpholinos; Avian Proteins; Proto-Oncogene Proteins c-myc; Neural crest; 03 medical and health sciences; Cell Movement; Animals; Biology (General); gene regulatory networks; Wnt Signaling Pathway; Neurons; SOXE Transcription Factors; Multipotent Stem Cells; Q; Neuropeptides; R; Gene Expression Regulation, Developmental; PAX7 Transcription Factor; RNA-Binding Proteins; Cell Differentiation; Forkhead Transcription Factors; multipotency; stem cell; Wnt Proteins; MicroRNAs; Neural Crest; Medicine; Developmental Biology

A crucial step in cell differentiation is the silencing of developmental programs underlying multipotency. While much is known about how lineage-specific genes are activated to generate distinct cell types, the mechanisms driving suppression of stemness are far less understood. To address this, we examined the regulation of the transcriptional network that maintains progenitor identity in avian neural crest cells. Our results show that a regulatory circuit formed by Wnt, Lin28a and let-7 miRNAs controls the deployment and the subsequent silencing of the multipotency program in a position-dependent manner. Transition from multipotency to differentiation is determined by the topological relationship between the migratory cells and the dorsal neural tube, which acts as a Wnt-producing stem cell niche. Our findings highlight a mechanism that rapidly silences complex regulatory programs, and elucidate how transcriptional networks respond to positional information during cell differentiation.