Abstract
The development of the embryonic brain critically depends on successfully completing cranial neural tube closure (NTC). Failure to properly close the neural tube results in significant and potentially lethal neural tube defects (NTDs). We believe these malformations are caused by disruptions in normal developmental programs such as those involved in neural plate morphogenesis and patterning, tissue fusion, and coordinated cell behaviors. Cranial NTDs include anencephaly and craniorachischisis, both lethal human birth defects. Newly emerging methods for molecular and cellular analysis offer a deeper understanding of not only the developmental NTC program itself but also mechanical and kinetic aspects of closure that may contribute to cranial NTDs. Clarifying the underlying mechanisms involved in NTC and how they relate to the onset of specific NTDs in various experimental models may help us develop novel intervention strategies to prevent NTDs.
Highlights
The process of cranial neural tube closure (NTC) creates the basic morphological scaffold for the central nervous system
Addition of blocking antibodies to N-cadherin or antisense-oligonucleotide against E-cadherin disrupts the cranial NTC in chicken and rat [105, 106]. These results suggest that proper regulation of these classic cadherins is indispensable for cranial NTC
Mice lacking intrinsic apoptotic pathway genes or harboring a mutant form of cytochrome-c that cannot activate apoptotic pathway but is intact for electron transport, or double-knockout mice for JNK1/JNK2 genes, exhibit cranial neural tube defects (NTDs), including exencephaly [119,120,121,122,123]. These results indicate that regulation of apoptosis is involved in successful cranial NTC
Summary
The process of cranial neural tube closure (NTC) creates the basic morphological scaffold for the central nervous system. Defects in this critical process result in lethal cranial neural tube defects (NTDs), most commonly expressed in humans as anencephaly. Miura and recent studies addressing the molecular and cellular mechanisms of cranial NTC in amniotes such as birds and mammals. As it is more feasible to perform experimental manipulation in order to dissect molecular and cellular pathways in chicken than in mouse, studies on the morphogenetic mechanisms using chicken as well as those using mice greatly help to increase our understanding of mammalian cranial NTC. Cranial NTC in mammals as well as in other vertebrates begins after neural induction that discriminates the neural plate from the adjacent surface ectoderm (Fig. 1a), and is achieved through sequential changes in the morphology of the neural plate as follows [2, 10]
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