Valerie Willocq
Valerie Willocq is a co-author of three Xenopus papers from Michael Levin's group on HCN channels. The first tested HCN4 in left-right organ patterning12. The next two used HCN2 to counter nicotine-induced brain defects, combining a computational model, voltage imaging and neural-targeted injections35.
- In the library
- 3 works
HCN4 and left-right asymmetry
In the 2017 paper, Willocq is one of several authors. The work asked whether HCN4 channel function matters for the placement of the heart and viscera. Embryos received HCN4-DN mRNA at the 2-cell stage, a condition that led to heterotaxia2. Injection after the second cleavage did not produce significant laterality defects, so the channel's activity was needed very early1. The authors also tested the link to the Nodal, Lefty and Pitx2 cascade by in situ hybridization, using the HCN inhibitor ZD7288 as a second manipulation2.
Nicotine model and voltage patterns
The 2018 paper set up an amphibian model of nicotine teratogenesis and used it to show how computational models can point to mechanisms and therapies3. In the model, leak permeabilities to K+ and Cl- produce a relatively hyperpolarized neural tube compared with the neural folds and ectoderm4. The predicted voltage patterns were then checked in embryos at stages 15 to 17. Voltage dye images were calibrated against whole-cell recordings from neural plate and flanking ectodermal cells5. Willocq appears among the authors of this work.
Rescue and later citation
The 2020 paper, with Willocq as co-author, tested where HCN2 must be expressed. Hcn2-WT mRNA injected into dorsal (neural) blastomeres protected against nicotine: 27% of tadpoles had brain defects. Dorsal injection alone gave 5%, not significantly different from controls6. The paper also cites the 2018 work, with other studies, for the view that correct voltage pre-patterns set by channel misexpression can rescue neural patterning defects from several causes7.
We conclude that HCN4 channel activity is involved in determining heart and visceral organ laterality; moreover, its activity must occur very early during cleavage stages
Pai VP, Willocq V, Pitcairn EJ, Lemire JM, Paré JF, Shi NQ…, 2017 · HCN4 ion channel function is required for early events that regulate anatomical… · open at passage 12Xenopus embryos were either injected with HCN4-DN mRNA in both blastomeres at 2-cell stage (the misexpression condition that leads to heterotaxia, Fig. 2)
Pai VP, Willocq V, Pitcairn EJ, Lemire JM, Paré JF, Shi NQ…, 2017 · HCN4 ion channel function is required for early events that regulate anatomical… · open at passage 14Here, we establish an amphibian model for nicotine teratogenesis, and exploit the Xenopus embryo as proof-of-principle of how computational models of physiological regulatory events can help identify mechanisms
Pai VP, Pietak A, Willocq V, Ye B, Shi NQ, Levin M, 2018 · HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns · open at passage 4creating the observed endogenous relative hyperpolarization in the neural tube compared to the neural folds and ectoderm.
Pai VP, Pietak A, Willocq V, Ye B, Shi NQ, Levin M, 2018 · HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns · open at passage 12Whole-cell electrophysiological recordings of Vmem from neural plate cells and flanking ectodermal cells were used as calibration points for the voltage reporter dye images
Pai VP, Pietak A, Willocq V, Ye B, Shi NQ, Levin M, 2018 · HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns · open at passage 20embryos with dorsal blastomere (neural) Hcn2-WT mRNA injection showed significant rescue or protection of nicotine-induced abnormal brain morphology (27% tadpoles with brain defects)
Pai VP, Cervera J, Mafe S, Willocq V, Lederer EK, Levin M, 2020 · HCN2 Channel-Induced Rescue of Brain Teratogenesis via Local and Long-Range… · open at passage 20establishing correct spatial membrane voltage pre patterns via misexpression of specific channels to control membrane voltage can rescue neural patterning defects caused by aberrant Notch signaling
Pai VP, Cervera J, Mafe S, Willocq V, Lederer EK, Levin M, 2020 · HCN2 Channel-Induced Rescue of Brain Teratogenesis via Local and Long-Range… · open at passage 4
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