scholarly journals Embryology of myelomeningocele and anencephaly

2004 ◽  
Vol 16 (2) ◽  
pp. 1-16 ◽  
Author(s):  
Mark S. Dias ◽  
Michael Partington
Keyword(s):  
Neural Tube ◽  
Neural Development ◽  
Conus Medullaris ◽  
Neural Tube Closure ◽  
Biomechanical Features ◽  
Early Human ◽  
Insight Into ◽  
Review Current ◽  
Tube Closure ◽  
Considerable Insight

The authors review current views on of the embryogenesis of the neural tube defects (NTDs) myelomeningocele and anencephaly. In this context, the following four approaches to the study of NTDs are discussed: normal morphogenesis and timing of early human neural development from conception to the ascent of the conus medullaris; mechanical and molecular biology of neural tube closure derived from experimental and animal models; morphological and biomechanical features of the NTDs myelomeningocele and anencephaly; and the experimental evidence for the importance of both genetic and environmental influences on human NTDs. Although considerable insight into both normal neural tube closure and the factor(s) by which this process may be disrupted has been reported in recent years, the exact mechanism(s) by which human myelomeningoceles and anencephaly arise remain elusive.

scholarly journals In utero gene transfer system for embryos before neural tube closure reveals a role for Hmga2 in the onset of neurogenesis

2020 ◽  
Author(s):  
Naohiro Kuwayama ◽  
Yusuke Kishi ◽  
Yurie Maeda ◽  
Yurie Nishiumi ◽  
Yutaka Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Tube ◽  
Neural Development ◽  
Viral Vectors ◽  
Early Stage ◽  
Cell Types ◽  
In Utero ◽  
Polycomb Group ◽  
Neural Tube Closure ◽  
Tube Closure

AbstractDuring the early stage of mammalian neural development, neuroepithelial cells (NECs) proliferate and increase their pool size before switching their fate to become neurogenic radial glial progenitors (RGPs). The timing of this expansion-to-neurogenic phase transition is strictly regulated so as to determine the proper number of progenitors and differentiated cell types that constitute the brain. The molecular mechanism underlying this switch has remained poorly understood, however, in part because of the difficulty associated with manipulation of gene expression in NECs before their transition to RGPs, which occurs before neural tube closure. We have now developed a simple and efficient method to manipulate gene expression in mouse neocortical NECs in the expansion phase by in utero injection of viral vectors at embryonic day 7.0 to 8.0. With the use of this method, we found that knockdown of the chromatin-associated protein Hmga2 in NECs inhibited the onset of the neurogenic phase in the neocortex. This effect of Hmga2 knockdown was accompanied by inhibition of the expression of a set of genes targeted by Polycomb group proteins, which repress neurogenic genes in cortical progenitors. Our study thus establishes a novel method for manipulation of gene expression in the early stage of mouse brain development as well as uncovers a key molecular player in the generation of neurogenic progenitors in the developing mouse neocortex.

scholarly journals Aberrant Gcm1 expression mediates Wnt/β-catenin pathway activation in folate deficiency involved in neural tube defects

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Jianting Li ◽  
Qiu Xie ◽  
Jun Gao ◽  
Fang Wang ◽  
Yihua Bao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neural Tube ◽  
Neural Development ◽  
Folate Deficiency ◽  
Early Embryo ◽  
Neural Tube Closure ◽  
Anteroposterior Patterning ◽  
T Cell Factor ◽  
Pathway Activation ◽  
Tube Closure

AbstractWnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway causes defective anteroposterior patterning, which results in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We have identified that folate deficiency activated Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promoted formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex formation to regulate the Wnt targeted gene transactivation through Wnt-responsive elements. Moreover, the transcription factor Nanog upregulated Gcm1 transcription in mESCs under folate deficiency. Lastly, in NTDs mouse models and low-folate NTDs human brain samples,Gcm1and Wnt/β-catenin targeted genes related to neural tube closure are specifically overexpressed. These results indicated that low-folate level promoted Wnt/β-catenin signaling via activating Gcm1, and thus leaded into aberrant vertebrate neural development.

scholarly journals Roles for Laminin in Embryogenesis: Exencephaly, Syndactyly, and Placentopathy in Mice Lacking the Laminin α5 Chain

1998 ◽  
Vol 143 (6) ◽  
pp. 1713-1723 ◽  
Author(s):  
Jeffrey H. Miner ◽  
Jeanette Cunningham ◽  
Joshua R. Sanes
Keyword(s):  
Embryonic Development ◽  
Neural Tube ◽  
Neural Tube Closure ◽  
Surface Ectoderm ◽  
Developmental Processes ◽  
Developmental Defects ◽  
Somite Stage ◽  
Development Proceeds ◽  
Insight Into ◽  
Tube Closure

Laminins are the major noncollagenous glycoproteins of all basal laminae (BLs). They are α/β/γ heterotrimers assembled from 10 known chains, and they subserve both structural and signaling roles. Previously described mutations in laminin chain genes result in diverse disorders that are manifested postnatally and therefore provide little insight into laminin's roles in embryonic development. Here, we show that the laminin α5 chain is required during embryogenesis. The α5 chain is present in virtually all BLs of early somite stage embryos and then becomes restricted to specific BLs as development proceeds, including those of the surface ectoderm and placental vasculature. BLs that lose α5 retain or acquire other α chains. Embryos lacking laminin α5 die late in embryogenesis. They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth. These defects are all attributable to defects in BLs that are α5 positive in controls and that appear ultrastructurally abnormal in its absence. Other laminin α chains accumulate in these BLs, but this compensation is apparently functionally inadequate. Our results identify new roles for laminins and BLs in diverse developmental processes.

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