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Concept: Neural groove

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During neural tube formation, neural plate cells migrate from the lateral aspects of the dorsal surface towards the midline. Elevation of the lateral regions of the neural plate produces the neural folds which then migrate to the midline where they fuse at their dorsal tips, generating a closed neural tube comprising an apicobasally polarized neuroepithelium. Our previous study identified a novel role for the axon guidance receptor neogenin in Xenopus neural tube formation. We demonstrated that loss of neogenin impeded neural fold apposition and neural tube closure. This study also revealed that neogenin, via its interaction with its ligand, RGMa, promoted cell-cell adhesion between neural plate cells as the neural folds elevated and between neuroepithelial cells within the neural tube. The second neogenin ligand, netrin-1, has been implicated in cell migration and epithelial morphogenesis. Therefore, we hypothesized that netrin-1 may also act as a ligand for neogenin during neurulation. Here we demonstrate that morpholino knockdown of Xenopus netrin-1 results in delayed neural fold apposition and neural tube closure. We further show that netrin-1 functions in the same pathway as neogenin and RGMa during neurulation. However, contrary to the role of neogenin-RGMa interactions, neogenin-netrin-1 interactions are not required for neural fold elevation or adhesion between neuroepithelial cells. Instead, our data suggest that netrin-1 contributes to the migration of the neural folds towards the midline. We conclude that both neogenin ligands work synergistically to ensure neural tube closure. © 2012 Wiley Periodicals, Inc., 2013.

Concepts: Axon, Embryology, Neural tube, Neurulation, Developmental neuroscience, Neural plate, Neural folds, Neural groove

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Neural tube (NT) formation in the spinal region of the mammalian embryo involves a wave of “zippering” that passes down the elongating spinal axis, uniting the neural fold tips in the dorsal midline. Failure of this closure process leads to open spina bifida, a common cause of severe neurologic disability in humans. Here, we combined a tissue-level strain-mapping workflow with laser ablation of live-imaged mouse embryos to investigate the biomechanics of mammalian spinal closure. Ablation of the zippering point at the embryonic dorsal midline causes far-reaching, rapid separation of the elevating neural folds. Strain analysis revealed tissue expansion around the zippering point after ablation, but predominant tissue constriction in the caudal and ventral neural plate zone. This zone is biomechanically coupled to the zippering point by a supracellular F-actin network, which includes an actin cable running along the neural fold tips. Pharmacologic inhibition of F-actin or laser ablation of the cable causes neural fold separation. At the most advanced somite stages, when completion of spinal closure is imminent, the cable forms a continuous ring around the neuropore, and simultaneously, a new caudal-to-rostral zippering point arises. Laser ablation of this new closure initiation point causes neural fold separation, demonstrating its biomechanical activity. Failure of spinal closure in pre-spina bifida Zic2(Ku) mutant embryos is associated with altered tissue biomechanics, as indicated by greater neuropore widening after ablation. Thus, this study identifies biomechanical coupling of the entire region of active spinal neurulation in the mouse embryo as a prerequisite for successful NT closure.

Concepts: Brain, Fetus, Embryology, Neural tube, Spina bifida, Neural plate, Neural folds, Neural groove

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The dorsal midline region of the neural tube that results from closure of the neural folds is generally termed the roof plate (RP). However, this domain is highly dynamic and complex, and is first transiently inhabited by prospective neural crest (NC) cells that sequentially emigrate from the neuroepithelium. It only later becomes the definitive RP, the dorsal midline cells of the spinal cord. We previously showed that at the trunk level of the axis, prospective RP progenitors originate ventral to the premigratory NC and progressively reach the dorsal midline following NC emigration. However, the molecular mechanisms underlying the end of NC production and formation of the definitive RP remain virtually unknown.

Concepts: Central nervous system, Spinal cord, Embryology, Dynamics, Neural tube, Axis powers, Neural groove, Alar plate

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Neural tube closure is an important morphogenetic event that involves dramatic reshaping of both neural and non-neural tissues. Rho GTPases are key cytoskeletal regulators involved in cell motility and in several developmental processes, and are thus expected to play pivotal roles in neurulation. Here, we discuss 2 recent studies that shed light on the roles of distinct Rho GTPases in different tissues during neurulation. RhoA plays an essential role in regulating actomyosin dynamics in the neural epithelium of the elevating neural folds, while Rac1 is required for the formation of cell protrusions in the non-neural surface ectoderm during neural fold fusion.

Concepts: Developmental biology, Animal, Embryology, Ectoderm, Neural tube, Neural plate, Neural folds, Neural groove

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Frontoethmoidal meningoencephalocele is a rare congenital malformation, which occurs due to a deficiency in neural tube closure. It may present as an external mass over the nose, nasal obstruction, rhinorrhea and attacks of central nervous system infections. Herein, the authors present a 3-month-old infant with naso-ethmoidal form of frontoethmoidal meningoencephalocele, who was operated on using a newly described approach that was performed under microscope.

Concepts: Central nervous system, Nervous system, Brain, Developmental biology, Congenital disorder, Neural tube, Congenital, Neural groove

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Neural tube defects (NTDs) are the most common congenital anomalies of the central nervous system. Prevalence of NTDs varies depending on geographic region and folic acid fortification. The main objectives of this study are to analyze the prevalences of NTDs reported to the National Registry of Congenital Anomalies of Argentina (RENAC) during the period 2009 to 2013, to compare them with data from other selected surveillance systems of the Americas, and to evaluate the impact of folic acid fortification on the prevalence of NTDs in Argentina.

Concepts: Central nervous system, Nervous system, Brain, Developmental biology, Folic acid, Glutamic acid, Neural tube, Neural groove

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Bending of the neural plate at paired dorsolateral hinge points (DLHPs) is required for neural tube closure in the spinal region of the mouse embryo. As a step towards understanding the morphogenetic mechanism of DLHP development, we examined variations in neural plate cellular architecture and proliferation during closure. Neuroepithelial cells within the median hinge point (MHP) contain nuclei that are mainly basally located and undergo relatively slow proliferation, with a 7h cell cycle length. In contrast, cells in the dorsolateral neuroepithelium, including the DLHP, exhibit nuclei distributed throughout the apico-basal axis and undergo rapid proliferation, with a 4h cell cycle length. As the neural folds elevate, cell numbers increase to a greater extent in the dorsolateral neural plate that contacts the surface ectoderm, compared with the more ventromedial neural plate where cells contact paraxial mesoderm and notochord. This marked increase in dorsolateral cell number cannot be accounted for solely on the basis of enhanced cell proliferation in this region. We hypothesised that neuroepithelial cells may translocate in a ventral-to-dorsal direction as DLHP formation occurs, and this was confirmed by vital cell labelling in cultured embryos. The translocation of cells into the neural fold, together with its more rapid cell proliferation, leads to an increase in cell density dorsolaterally compared with the more ventromedial neural plate. These findings suggest a model in which DLHP formation may proceed through ‘buckling’ of the neuroepithelium at a dorso-ventral boundary marked by a change in cell-packing density.

Concepts: Cell nucleus, Embryo, Developmental biology, Embryology, Neural tube, Neural plate, Neural folds, Neural groove

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Newborns with a myelomeningocele are often brought to the operating room for surgical repair within the first few days of life. Wound infection in this population may represent a devastating outcome in the immature nervous system. No studies have evaluated infection as a function of surgical timing at a national level. We hypothesized an increase in wound infection in those patients with delays in myelomeningocele repair when evaluated from a national database.

Concepts: Central nervous system, Nervous system, Brain, Neural groove

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Unidirectional zippering is a key step in neural tube closure that remains poorly understood. Here, we combine experimental and computational approaches to identify the mechanism for zippering in a basal chordate, Ciona intestinalis. We show that myosin II is activated sequentially from posterior to anterior along the neural/epidermal (Ne/Epi) boundary just ahead of the advancing zipper. This promotes rapid shortening of Ne/Epi junctions, driving the zipper forward and drawing the neural folds together. Cell contact rearrangements (Ne/Epi + Ne/Epi → Ne/Ne + Epi/Epi) just behind the zipper lower tissue resistance to zipper progression by allowing transiently stretched cells to detach and relax toward isodiametric shapes. Computer simulations show that measured differences in junction tension, timing of primary contractions, and delay before cell detachment are sufficient to explain the speed and direction of zipper progression and highlight key advantages of a sequential contraction mechanism for robust efficient zippering.

Concepts: Central nervous system, Protein, Brain, Cerebrum, Neural tube, Ciona intestinalis, Tunicate, Neural groove

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Neural tube dysraphisms are congenital anomalies resulting from impaired formation of structures along the craniospinal axis during central nervous system development. When these malformations are large or lack a skin covering, they are easily recognized, whereas smaller or skin-covered malformations may not be readily apparent. Due to the intimate embryologic origin of the skin and nervous system, these occult malformations are often heralded by associated cutaneous abnormalities. In this article, the common clinical presentations and cutaneous markers of craniospinal dysraphism are reviewed, along with the recommended imaging modalities.

Concepts: Central nervous system, Nervous system, Psychology, Brain, Developmental biology, Skin, Congenital disorder, Neural groove