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PMID:23014696

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Citation

Su, CY, Bay, SN, Mariani, LE, Hillman, MJ and Caspary, T (2012) Temporal deletion of Arl13b reveals that a mispatterned neural tube corrects cell fate over time. Development 139:4062-71

Abstract

Cilia are necessary for sonic hedgehog (Shh) signaling, which is required to pattern the neural tube. We know that ventral neural cell fates are defined by a specific cohort of transcription factors that are induced by distinct thresholds of Shh activity mediated by opposing gradients of Gli activator (GliA) and Gli repressor (GliR). Despite this understanding, the role of Shh as an instructive morphogen is viewed as increasingly complex, with current models integrating positive inputs in terms of ligand concentration and time, along with negative feedback via the downstream gene regulatory network. To investigate the relative contributions of the positive and negative inputs from Shh signaling in neural patterning, we took advantage of a protein that uncouples the regulation of GliA and GliR: the cilia protein ADP-ribosylation factor-like 13b (Arl13b). By deleting Arl13b in mouse, we induced low-level constitutive GliA function at specific developmental stages and defined a crucial period prior to E10.5 when shifts in the level of GliA cause cells to change their fate. Strikingly, we found that improperly patterned cells in these mice converted to the wild-type pattern by E12.5. We further showed that the recovery of patterning did not occur when we also deleted Gli3, the primary GliR in the neural tube, revealing a crucial role of Gli3 in the maintenance of neural patterning.

Links

PubMed PMC3472586 Online version:10.1242/dev.082321

Keywords

ADP-Ribosylation Factors/genetics; ADP-Ribosylation Factors/metabolism; Animals; Blotting, Western; Body Patterning/genetics; Body Patterning/physiology; Cells, Cultured; Cilia/metabolism; Hedgehog Proteins/genetics; Hedgehog Proteins/metabolism; Mice; Mice, Mutant Strains; Neural Tube/embryology; Neural Tube/metabolism; Real-Time Polymerase Chain Reaction; Receptors, G-Protein-Coupled/genetics; Receptors, G-Protein-Coupled/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:AR13B

involved_in

GO:0021532: neural tube patterning

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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