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PLoS Genet DOI:10.1371/journal.pgen.1002762

Attenuation of Notch and Hedgehog signaling is required for fate specification in the spinal cord.

Publication TypeJournal Article
Year of Publication2012
AuthorsHuang, P, Xiong, F, Megason, SG, Schier, AF
JournalPLoS Genet
Date Published2012
KeywordsAnimals, Animals, Genetically Modified, Cell Differentiation, Cell Division, Cell Lineage, Embryonic Development, Gene Expression Regulation, Developmental, Hedgehog Proteins, Interneurons, Patched Receptors, Receptors, Cell Surface, Receptors, Notch, Signal Transduction, Spinal Cord, Stem Cells, Zebrafish

During the development of the spinal cord, proliferative neural progenitors differentiate into postmitotic neurons with distinct fates. How cells switch from progenitor states to differentiated fates is poorly understood. To address this question, we studied the differentiation of progenitors in the zebrafish spinal cord, focusing on the differentiation of Kolmer-Agduhr″ (KA″) interneurons from lateral floor plate (LFP) progenitors. In vivo cell tracking demonstrates that KA″ cells are generated from LFP progenitors by both symmetric and asymmetric cell divisions. A photoconvertible reporter of signaling history (PHRESH) reveals distinct temporal profiles of Hh response: LFP progenitors continuously respond to Hh, while KA″ cells lose Hh response upon differentiation. Hh signaling is required in LFP progenitors for KA″ fate specification, but prolonged Hh signaling interferes with KA″ differentiation. Notch signaling acts permissively to maintain LFP progenitor cells: activation of Notch signaling prevents differentiation, whereas inhibition of Notch signaling results in differentiation of ectopic KA″ cells. These results indicate that neural progenitors depend on Notch signaling to maintain Hh responsiveness and rely on Hh signaling to induce fate identity, whereas proper differentiation depends on the attenuation of both Notch and Hh signaling.


Alternate JournalPLoS Genet.
PubMed ID22685423
PubMed Central IDPMC3369957
Grant ListR01 DE016779 / DE / NIDCR NIH HHS / United States
R01 GM056211 / GM / NIGMS NIH HHS / United States
5R01DE016779 / DE / NIDCR NIH HHS / United States