Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies

UBC Faculty Research and Publications

Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies Juriloff, Diana M.; Harris, Muriel J.

Abstract

The human neural tube defects (NTD), anencephaly, spina bifida and craniorachischisis, originate from a failure of the embryonic neural tube to close. Human NTD are relatively common and both complex and heterogeneous in genetic origin, but the genetic variants and developmental mechanisms are largely unknown. Here we review the numerous studies, mainly in mice, of normal neural tube closure, the mechanisms of failure caused by specific gene mutations, and the evolution of the vertebrate cranial neural tube and its genetic processes, seeking insights into the etiology of human NTD. We find evidence of many regions along the anterior–posterior axis each differing in some aspect of neural tube closure—morphology, cell behavior, specific genes required—and conclude that the etiology of NTD is likely to be partly specific to the anterior–posterior location of the defect and also genetically heterogeneous. We revisit the hypotheses explaining the excess of females among cranial NTD cases in mice and humans and new developments in understanding the role of the folate pathway in NTD. Finally, we demonstrate that evidence from mouse mutants strongly supports the search for digenic or oligogenic etiology in human NTD of all types.

Item Metadata

Title	Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies
Creator	Juriloff, Diana M.; Harris, Muriel J.
Publisher	Multidisciplinary Digital Publishing Institute
Date Issued	2018-08-21
Description	The human neural tube defects (NTD), anencephaly, spina bifida and craniorachischisis, originate from a failure of the embryonic neural tube to close. Human NTD are relatively common and both complex and heterogeneous in genetic origin, but the genetic variants and developmental mechanisms are largely unknown. Here we review the numerous studies, mainly in mice, of normal neural tube closure, the mechanisms of failure caused by specific gene mutations, and the evolution of the vertebrate cranial neural tube and its genetic processes, seeking insights into the etiology of human NTD. We find evidence of many regions along the anterior–posterior axis each differing in some aspect of neural tube closure—morphology, cell behavior, specific genes required—and conclude that the etiology of NTD is likely to be partly specific to the anterior–posterior location of the defect and also genetically heterogeneous. We revisit the hypotheses explaining the excess of females among cranial NTD cases in mice and humans and new developments in understanding the role of the folate pathway in NTD. Finally, we demonstrate that evidence from mouse mutants strongly supports the search for digenic or oligogenic etiology in human NTD of all types.
Subject	Neural tube; Neural folds; Anencephaly; Exencephaly; Spina bifida; Craniorachischisis; Folate; Epigenetics; Developmental genetics
Genre	Article
Type	Text
Language	eng
Date Available	2019-06-21
Provider	Vancouver : University of British Columbia Library
Rights	CC BY 4.0
DOI	10.14288/1.0379525
URI	http://hdl.handle.net/2429/70731
Affiliation	Medicine, Faculty of; Medical Genetics, Department of
Citation	Journal of Developmental Biology 6 (3): 22 (2018)
Publisher DOI	10.3390/jdb6030022
Peer Review Status	Reviewed
Scholarly Level	Faculty
Rights URI	https://creativecommons.org/licenses/by/4.0/
Aggregated Source Repository	DSpace

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