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Planar cell polarity genes and neural tube closure
Naoto Ueno1, Nicholas D E Greene
1Department of Developmental Biology, National Institute for Basic Biology, and SOKENDAI, Okazaki, Japan. nueno@nibb.ac.jp
Abstract:
Closure of the neural tube is essential for normal development of the brain and spinal cord. Failure of closure results in neural tube defects (NTDs), common and clinically severe congenital malformations whose molecular mechanisms remain poorly understood. On the other hand, it is increasingly well established that common molecular mechanisms are employed to regulate morphogenesis of multicellular organisms. For example, signaling triggered by polypeptide growth factors is highly conserved among species and utilized in multiple developmental processes. Recent studies have revealed that the Drosophila planar cell polarity (PCP) pathway, which directs position and direction of wing hairs on the surface of the fly wing, is well conserved, and orthologs of several genes encoding components of the pathway are also found in vertebrates. Interestingly, in vertebrates, this signaling pathway appears to be co-opted to regulate "convergent extension" cell movements during gastrulation. Disruption of vertebrate PCP genes in Xenopus laevis or zebrafish causes severe gastrulation defects or the shortening of the trunk, as well as mediolateral expansion of somites. In Xenopus, in which the neural tube closes by elevation and fusion of neural folds, inhibition of convergent extension can also prevent neural tube closure causing a "spina bifida-like" appearance. Furthermore, several of the genes involved in the PCP pathway have recently been shown to be required for neural tube closure in the mouse, since mutation of these genes causes NTDs. Therefore, understanding the mechanisms underlying the establishment of cell polarity in Drosophila may provide important clues to the molecular basis of NTDs.
Insights
Neural tube defects (NTDs) are severe congenital malformations. Research suggests the conserved planar cell polarity (PCP) pathway, crucial for cell orientation, may offer insights into NTD molecular mechanisms.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Neural tube closure is critical for central nervous system development.
- Failure leads to neural tube defects (NTDs), common congenital malformations with poorly understood molecular causes.
- Multicellular morphogenesis often involves conserved molecular mechanisms, including growth factor signaling.
Purpose of the Study:
- To explore the role of the conserved planar cell polarity (PCP) pathway in neural tube closure.
- To investigate potential links between PCP pathway function and the molecular basis of neural tube defects (NTDs).
Main Methods:
- Comparative analysis of the planar cell polarity (PCP) pathway in Drosophila and vertebrates.
- Examination of PCP gene function in vertebrate models (Xenopus laevis, zebrafish) and mouse models.
- Investigating the impact of inhibiting convergent extension cell movements on neural tube closure.
Main Results:
- The planar cell polarity (PCP) pathway, conserved across species, regulates cell polarity and morphogenesis.
- In vertebrates, PCP signaling is involved in convergent extension cell movements during gastrulation.
- Disruption of PCP genes in Xenopus and zebrafish causes gastrulation defects and trunk shortening.
- Inhibition of convergent extension in Xenopus leads to a "spina bifida-like" phenotype.
- Mutations in PCP pathway genes in mice result in neural tube defects (NTDs).
Conclusions:
- The conserved planar cell polarity (PCP) pathway plays a critical role in vertebrate neural tube closure.
- Understanding PCP mechanisms in simpler organisms like Drosophila may provide crucial insights into the molecular etiology of human neural tube defects (NTDs).