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Dev Dyn. 2018 Jan;247(1):170-184. doi: 10.1002/dvdy.24590. Epub 2017 Oct 17.

Ventral neural patterning in the absence of a Shh activity gradient from the floorplate.

Author information

1
Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, and Brain Repair Centre, Life Sciences Research Institute, Halifax, Nova Scotia, Canada.
2
Doshisha University, Graduate School of Brain Science, Kyotanabe, Kyoto, Japan.
3
Department of Orthodontics and Dentofacial Orthopedics, Graduate School of Dentistry, Osaka University, Osaka, Japan.
4
Stowers Institute For Medical Research, Kansas City, Missouri.
5
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas.

Abstract

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 naïve 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 (HhatCreface ) 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 (Ptch1Wig ) that is unable to inhibit Shh signal transduction, resulting in expanded ventral progenitor domains. Surprisingly, HhatCreface/Creface ; Ptch1Wig/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. © 2017 Wiley Periodicals, Inc.

KEYWORDS:

Hedgehog acetyltransferace; Patched1; Sonic hedgehog; floorplate; morphogen gradient; neural patterning; notochord

PMID:
28891097
PMCID:
PMC5739940
[Available on 2019-01-01]
DOI:
10.1002/dvdy.24590
[Indexed for MEDLINE]

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