Closed spinal dysraphisms are poorly understood malformations classified as neural tube (NT) defects. Several, including terminal myelocystocele, affect the distal spine. We have previously identified a NT closure-initiating point, Closure 5, in the distal spine of mice. Here, we document equivalent morphology of the caudal-most closing posterior neuropore (PNP) in mice and humans. Closure 5 forms in a region of active FGF signalling, and pharmacological FGF receptor blockade impairs its formation in cultured mouse embryos. Conditional genetic deletion of Fgfr1 in caudal embryonic tissues with Cdx2Cre diminishes neuroepithelial proliferation, impairs Closure 5 formation and delays PNP closure. After closure, the distal NT of Fgfr1-disrupted embryos dilates to form a fluid-filled sac overlying ventrally flattened spinal cord. This phenotype resembles terminal myelocystocele. Histological analysis reveals regional and progressive loss of SHH- and FOXA2-positive ventral NT domains, resulting in OLIG2 labelling of the ventral-most NT. The OLIG2 domain is also subsequently lost, eventually producing a NT that is entirely positive for the dorsal marker PAX3. Thus, a terminal myelocystocele-like phenotype can arise after completion of NT closure with localised spinal mis-patterning caused by disruption of FGFR1 signalling.
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http://dx.doi.org/10.1242/dev.202139 | DOI Listing |
World Neurosurg
December 2024
Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, P.R. China. Electronic address:
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Department of Hemato-Oncology, Chungnam National University Hospital, Dajeon, Republic of Korea.
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View Article and Find Full Text PDFMedicine (Baltimore)
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Department of Neurosurgery, Hacettepe University Faculty of Medicine, Ankara, Turkey.
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View Article and Find Full Text PDFMedicine (Baltimore)
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Department of Pharmacy, Zibo Hospital of Traditional Chinese Medicine, Zibo City, Shandong Province, China.
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View Article and Find Full Text PDFMedicine (Baltimore)
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Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
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