Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies
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 large...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-08-01
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| Series: | Journal of Developmental Biology |
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| Online Access: | http://www.mdpi.com/2221-3759/6/3/22 |
| _version_ | 1819081325604241408 |
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| author | Diana M. Juriloff Muriel J. Harris |
| author_facet | Diana M. Juriloff Muriel J. Harris |
| author_sort | Diana M. Juriloff |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T19:58:59Z |
| format | Article |
| id | doaj.art-58d8fcfe97ea42498894ca30f11eacad |
| institution | Directory Open Access Journal |
| issn | 2221-3759 |
| language | English |
| last_indexed | 2024-12-21T19:58:59Z |
| publishDate | 2018-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Developmental Biology |
| spelling | doaj.art-58d8fcfe97ea42498894ca30f11eacad2022-12-21T18:52:01ZengMDPI AGJournal of Developmental Biology2221-37592018-08-01632210.3390/jdb6030022jdb6030022Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary StudiesDiana M. Juriloff0Muriel J. Harris1Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaDepartment of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, CanadaThe 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.http://www.mdpi.com/2221-3759/6/3/22neural tubeneural foldsanencephalyexencephalyspina bifidacraniorachischisisfolateepigeneticsdevelopmental genetics |
| spellingShingle | Diana M. Juriloff Muriel J. Harris Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies Journal of Developmental Biology neural tube neural folds anencephaly exencephaly spina bifida craniorachischisis folate epigenetics developmental genetics |
| title | Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies |
| title_full | Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies |
| title_fullStr | Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies |
| title_full_unstemmed | Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies |
| title_short | Insights into the Etiology of Mammalian Neural Tube Closure Defects from Developmental, Genetic and Evolutionary Studies |
| title_sort | insights into the etiology of mammalian neural tube closure defects from developmental genetic and evolutionary studies |
| topic | neural tube neural folds anencephaly exencephaly spina bifida craniorachischisis folate epigenetics developmental genetics |
| url | http://www.mdpi.com/2221-3759/6/3/22 |
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