Journal
DEVELOPMENTAL DYNAMICS
Volume 247, Issue 1, Pages 170-184Publisher
WILEY
DOI: 10.1002/dvdy.24590
Keywords
Sonic hedgehog; morphogen gradient; Hedgehog acetyltransferace; Patched1; neural patterning; floorplate; notochord
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Funding
- Natural Sciences and Engineering Council of Canada [RGPIN-2015-04475]
- Plum Foundation
- Stowers Institute for Medical Research
- National Institutes of Dental and Craniofacial Research [DE016082]
- NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH [R01DE016082] Funding Source: NIH RePORTER
- Grants-in-Aid for Scientific Research [15K07084] Funding Source: KAKEN
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Background: Vertebrate spinal cord development requires Sonic Hedgehog (Shh) signaling from the floorplate and notochord, where it is thought to act in concentration dependent manner to pattern distinct cell identities along the ventral-to-dorsal axis. While in vitro experiments demonstrate naive neural tissues are sensitive to small changes in Shh levels, genetic studies illustrate that some degree of ventral patterning can occur despite significant perturbations in Shh signaling. Consequently, the mechanistic relationship between Shh morphogen levels and acquisition of distinct cell identities remains unclear. Results: We addressed this using Hedgehog acetyltransferase (Hhat(Creface)) and Wiggable mouse mutants. Hhat encodes a palmitoylase required for the secretion of Hedgehog proteins and formation of the Shh gradient. In its absence, the spinal cord develops without floorplate cells and V3 interneurons. Wiggable is an allele of the Shh receptor Patched1 (Ptch1(Wig)) that is unable to inhibit Shh signal transduction, resulting in expanded ventral progenitor domains. Surprisingly, Hhat(Creface/Creface); Ptch1(Wig/Wig) double mutants displayed fully restored ventral patterning despite an absence of Shh secretion from the floorplate. Conclusions: The full range of neuronal progenitor types can be generated in the absence of a Shh gradient provided pathway repression is dampened, illustrating the complexity of morphogen dynamics in vertebrate patterning. Developmental Dynamics 247:170-184, 2018. (C) 2017 Wiley Periodicals, Inc.
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