Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure

Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here, we show that this process involves a tissue-wide pattern of apical constriction controll...

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Bibliographic Details
Published ineLife Vol. 9
Main Authors Brooks, Eric R, Islam, Mohammed Tarek, Anderson, Kathryn V, Zallen, Jennifer A
Format Journal Article
LanguageEnglish
Published England eLife Science Publications, Ltd 26.10.2020
eLife Sciences Publications, Ltd
eLife Sciences Publications Ltd
Subjects
Animals
apical constriction
Brain - embryology
Cell Biology
Cell Shape
Cellular signal transduction
cilia
Developmental Biology
exencephaly
Hedgehog Proteins - metabolism
Hedgehog Proteins - physiology
Mesencephalon
Mice
Mice, Inbred C57BL
morphogenesis
Neural Crest - embryology
Neural tube
Neural Tube - embryology
Neural Tube - growth & development
neural tube defects
Observations
Physiological aspects
Sonic hedgehog
United States
apical constriction
mouse
cell biology
morphogenesis
developmental biology
sonic hedgehog
cilia
neural tube defects
exencephaly
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Summary:Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here, we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are flat with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutants and and embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.
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ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.60234