scholarly journals Distinct spatiotemporal contribution of morphogenetic events and mechanical tissue coupling during Xenopus neural tube closure

2021 ◽  
Author(s):  
Neophytos Christodoulou ◽  
Paris Alexander Skourides
Keyword(s):  
Neural Tube ◽  
Cell Tracking ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Loss Of Function ◽  
Surface Ectoderm ◽  
Apical Constriction ◽  
The Central Nervous System ◽  
Resistive Forces ◽  
Tube Closure

Neural tube closure (NTC) is a fundamental process during vertebrate embryonic development and is indispensable for the formation of the central nervous system. Here, using Xenopus laevis embryos, live imaging, single-cell tracking, optogenetics, and loss of function experiments we examine the contribution of convergent extension (CE) and apical constriction (AC) and we define the role of the surface ectoderm (SE) during NTC. We show that NTC is a two-stage process and that CE and AC do not overlap temporally while their spatial activity is distinct. PCP-driven CE is restricted to the caudal part of the neural plate (NP) and takes place during the first stage. CE is essential for correct positioning of the NP rostral most region in the midline of the dorsoventral axis. AC occurs after CE throughout the NP and is the sole contributor of anterior NTC. We go on to show that the SE is mechanically coupled with the NP providing resistive forces during NTC. Its movement towards the midline is passive and driven by forces generated through NP morphogenesis. Last, we show that increase of SE resistive forces is detrimental for NP morphogenesis, showing that correct SE development is permissive for NTC.

scholarly journals Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds

Development ◽  
2021 ◽  
Vol 148 (2) ◽  
pp. dev195008
Author(s):  
Izabela Kowalczyk ◽  
Chanjae Lee ◽  
Elisabeth Schuster ◽  
Josefine Hoeren ◽  
Valentina Trivigno ◽  
...  
Keyword(s):  
Neural Tube ◽  
Planar Cell Polarity ◽  
Adaptor Proteins ◽  
Tube Formation ◽  
Neural Tube Closure ◽  
Model Organisms ◽  
Loss Of Function ◽  
Functional Interaction ◽  
Apical Constriction ◽  
Tube Closure

ABSTRACTPathogenic mutations in the endocytic receptor LRP2 in humans are associated with severe neural tube closure defects (NTDs) such as anencephaly and spina bifida. Here, we have combined analysis of neural tube closure in mouse and in the African Clawed Frog Xenopus laevis to elucidate the etiology of Lrp2-related NTDs. Lrp2 loss of function impaired neuroepithelial morphogenesis, culminating in NTDs that impeded anterior neural plate folding and neural tube closure in both model organisms. Loss of Lrp2 severely affected apical constriction as well as proper localization of the core planar cell polarity (PCP) protein Vangl2, demonstrating a highly conserved role of the receptor in these processes, which are essential for neural tube formation. In addition, we identified a novel functional interaction of Lrp2 with the intracellular adaptor proteins Shroom3 and Gipc1 in the developing forebrain. Our data suggest that, during neurulation, motifs within the intracellular domain of Lrp2 function as a hub that orchestrates endocytic membrane removal for efficient apical constriction, as well as PCP component trafficking in a temporospatial manner.

Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds

2020 ◽  
Author(s):  
Izabela Kowalczyk ◽  
Chanjae Lee ◽  
Elisabeth Schuster ◽  
Josefine Hoeren ◽  
Valentina Trivigno ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Planar Cell Polarity ◽  
Adaptor Proteins ◽  
Neural Tube Closure ◽  
Model Organisms ◽  
Loss Of Function ◽  
Functional Interaction ◽  
Apical Constriction ◽  
Tube Closure

AbstractRecent studies have revealed that pathogenic mutations in the endocytic receptor LRP2 in humans are associated with severe neural tube closure defects (NTDs) such as anencephaly and spina bifida. Here, we combined analysis of neural tube closure in mouse and in the African Clawed Frog Xenopus laevis to elucidate the etiology of Lrp2-related NTDs. Lrp2 loss-of-function (LOF) impaired neuroepithelial morphogenesis, culminating in NTDs that impeded anterior neural plate folding and neural tube closure in both model organisms. Loss of Lrp2 severely affected apical constriction as well as proper localization of the core planar cell polarity (PCP) protein Vangl2, demonstrating a highly conserved role of the receptor in these processes essential for neural tube formation. In addition, we identified a novel functional interaction of Lrp2 with the intracellular adaptor proteins Shroom3 and Gipc1 in the developing forebrain. Our data suggest that during neurulation, motifs within the intracellular domain of Lrp2 function as a hub that orchestrates endocytic membrane removal for efficient apical constriction as well as PCP component trafficking in a temporospatial manner.Summary statementAnalysis of neurulation in mouse and Xenopus reveals novel roles for Lrp2-mediated endocytosis in orchestrating apical constriction and planar cell polarity essential for neural tube closure.

scholarly journals A loss-of-function NUAK2 mutation in humans causes anencephaly due to impaired Hippo-YAP signaling

2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Carine Bonnard ◽  
Naveenan Navaratnam ◽  
Kakaly Ghosh ◽  
Puck Wee Chan ◽  
Thong Teck Tan ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Progenitor Cells ◽  
Neural Tube Closure ◽  
Hippo Signaling ◽  
Loss Of Function ◽  
Serine Threonine Kinase ◽  
Apical Constriction ◽  
Signaling Axis ◽  
Tube Closure

Failure of neural tube closure during embryonic development can result in anencephaly, one of the most common birth defects in humans. A family with recurrent anencephalic fetuses was investigated to understand its etiology and pathogenesis. Exome sequencing revealed a recessive germline 21-bp in-frame deletion in NUAK2 segregating with the disease. In vitro kinase assays demonstrated that the 7–amino acid truncation in NUAK2, a serine/threonine kinase, completely abrogated its catalytic activity. Patient-derived disease models including neural progenitor cells and cerebral organoids showed that loss of NUAK2 activity led to decreased Hippo signaling via cytoplasmic YAP retention. In neural tube–like structures, endogenous NUAK2 colocalized apically with the actomyosin network, which was disrupted in patient cells, causing impaired nucleokinesis and apical constriction. Our results establish NUAK2 as an indispensable kinase for brain development in humans and suggest that a NUAK2-Hippo signaling axis regulates cytoskeletal processes that govern cell shape during neural tube closure.

scholarly journals Lulu Regulates Shroom-Induced Apical Constriction during Neural Tube Closure

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e81854 ◽  
Author(s):  
Chih-Wen Chu ◽  
Emma Gerstenzang ◽  
Olga Ossipova ◽  
Sergei Y. Sokol
Keyword(s):  
Neural Tube ◽  
Neural Tube Closure ◽  
Apical Constriction ◽  
Tube Closure

scholarly journals Distinct intracellular Ca2+dynamics regulate apical constriction and differentially contribute to neural tube closure

Development ◽  
2017 ◽  
Vol 144 (7) ◽  
pp. 1307-1316 ◽  
Author(s):  
Makoto Suzuki ◽  
Masanao Sato ◽  
Hiroshi Koyama ◽  
Yusuke Hara ◽  
Kentaro Hayashi ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Closure ◽  
Apical Constriction ◽  
Tube Closure

scholarly journals Claudins are essential for cell shape changes and convergent extension movements during neural tube closure

2017 ◽  
Vol 428 (1) ◽  
pp. 25-38 ◽  
Author(s):  
Amanda I. Baumholtz ◽  
Annie Simard ◽  
Evanthia Nikolopoulou ◽  
Marcus Oosenbrug ◽  
Michelle M. Collins ◽  
...  
Keyword(s):  
Neural Tube ◽  
Cell Shape ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Cell Shape Changes ◽  
Shape Changes ◽  
Tube Closure

scholarly journals Shroom Induces Apical Constriction and Is Required for Hingepoint Formation during Neural Tube Closure

2003 ◽  
Vol 13 (24) ◽  
pp. 2125-2137 ◽  
Author(s):  
Saori L. Haigo ◽  
Jeffrey D. Hildebrand ◽  
Richard M. Harland ◽  
John B. Wallingford
Keyword(s):  
Neural Tube ◽  
Neural Tube Closure ◽  
Apical Constriction ◽  
Tube Closure

Dishevelled: linking convergent extension with neural tube closure

2003 ◽  
Vol 26 (9) ◽  
pp. 453-455 ◽  
Author(s):  
Andrew J Copp ◽  
Nicholas D.E Greene ◽  
Jennifer N Murdoch
Keyword(s):  
Neural Tube ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Tube Closure

scholarly journals Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure

2020 ◽  
Author(s):  
Eric R. Brooks ◽  
Mohammed T. Islam ◽  
Kathryn V. Anderson ◽  
Jennifer A. Zallen
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Structural Changes ◽  
Neural Tube Closure ◽  
Mammalian Brain ◽  
Shh Signaling ◽  
Apical Constriction ◽  
Cell Remodeling ◽  
Tube Closure

AbstractNeural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are short with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutants Ift122 and Ttc21b and embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.

scholarly journals Hingepoints and neural folds reveal conserved features of primary neurulation in the zebrafish forebrain

2019 ◽  
Author(s):  
Jonathan M. Werner ◽  
Maraki Y. Negesse ◽  
Dominique L. Brooks ◽  
Allyson R. Caldwell ◽  
Jafira M. Johnson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Neural Tube ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Developmental Studies ◽  
Underlying Causes ◽  
The Central Nervous System ◽  
Neural Tube Development ◽  
Fold Formation ◽  
Tube Closure

ABSTRACTPrimary neurulation is the process by which the neural tube, the central nervous system precursor, is formed from the neural plate. Incomplete neural tube closure occurs frequently, yet underlying causes remain poorly understood. Developmental studies in amniotes and amphibians have identified hingepoint and neural fold formation as key morphogenetic events and hallmarks of primary neurulation, the disruption of which causes neural tube defects. In contrast, the mode of neurulation in teleosts such as zebrafish has remained highly debated. Teleosts are thought to have evolved a unique pattern of neurulation, whereby the neural plate infolds in absence of hingepoints and neural folds (NFs), at least in the hindbrain/trunk where it has been studied. We report here on zebrafish forebrain morphogenesis where we identify these morphological landmarks. Our findings reveal a deeper level of conservation of neurulation than previously recognized and establish the zebrafish as a model to understand human neural tube development.

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