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<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="HvQ6pN7HbBZiXvC7y6NK5O0hHXKV9ALkYiAb2DA3LcMMRWIXbpqMzWwVf1s72bjE">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="HvQ6pN7HbBZiXvC7y6NK5O0hHXKV9ALkYiAb2DA3LcMMRWIXbpqMzWwVf1s72bjE">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="HvQ6pN7HbBZiXvC7y6NK5O0hHXKV9ALkYiAb2DA3LcMMRWIXbpqMzWwVf1s72bjE">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="HvQ6pN7HbBZiXvC7y6NK5O0hHXKV9ALkYiAb2DA3LcMMRWIXbpqMzWwVf1s72bjE">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="HvQ6pN7HbBZiXvC7y6NK5O0hHXKV9ALkYiAb2DA3LcMMRWIXbpqMzWwVf1s72bjE">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="23549079">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1172/JCI66903"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=6619&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=23549079&amp;db=pubmed&amp;nlmid=7802877"
title="See full text options at American Society for Clinical Investigation"
data-ga-category="full_text"
data-ga-action="American Society for Clinical Investigation"
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><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--dm5migu4zj3pb.cloudfront.net-images-pubmed-jci_full_text_link_out.jpg" alt="American Society for Clinical Investigation full text link"><span class="text">
American Society for Clinical Investigation
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/23549079/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=23549079&amp;db=pubmed&amp;nlmid=7802877"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="23549079"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/23549079/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/23549079/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="23549079" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23549079%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="HvQ6pN7HbBZiXvC7y6NK5O0hHXKV9ALkYiAb2DA3LcMMRWIXbpqMzWwVf1s72bjE"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
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<p>
The identification of a gain-of-function mutation in CACNA1C as the cause of Timothy Syndrome (TS), a rare disorder characterized by cardiac arrhythmias and syndactyly, highlighted unexpected roles for the L-type voltage-gated Ca2+ channel CaV1.2 in nonexcitable cells. How abnormal Ca2+ influx through CaV1.2 underlies phenotypes such as the accompanying syndactyly or craniofacial abnormalities in the majority of affected individuals is not readily explained by established CaV1.2 roles. Here, we show that CaV1.2 is expressed in the first and second pharyngeal arches within the subset of cells that give rise to jaw primordia. Gain-of-function and loss-of-function studies in mouse, in concert with knockdown/rescue and pharmacological approaches in zebrafish, demonstrated that Ca2+ influx through CaV1.2 regulates jaw development. Cranial neural crest migration was unaffected by CaV1.2 knockdown, suggesting a role for CaV1.2 later in development. Focusing on the mandible, we observed that cellular hypertrophy and hyperplasia depended upon Ca2+ signals through CaV1.2, including those that activated the calcineurin signaling pathway. Together, these results provide new insights into the role of voltage-gated Ca2+ channels in nonexcitable cells during development.
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data-image-width="672"
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data-pmc-id="PMC3613930"
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
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<p> Figure 1. Ca <sub> V </sub> 1.2 is expressed… </p>
</strong>
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<strong class="figure-label">
<p> Figure 1. Ca <sub> V </sub> 1.2 is expressed in developing jaw. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> <b> D </b> ) Whole-mount β-gal… </p></div>
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<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Figure 1. Ca<sub>V</sub>1.2 is expressed in developing jaw.
</strong>
<div class="figure-caption-contents">(<b>A</b><b>D</b>) Whole-mount β-gal staining of <i>Ca<sub>V</sub>1.2<sup>+/LacZ</sup></i> embryos. Ca<sub>V</sub>1.2 is highly expressed in the developing heart around E9.5 (<b>A</b>). By E11.5 intense staining is present in the first (arrowhead) and second (arrow) pharyngeal arches (<b>B</b><b>D</b>). (<b>E</b> and <b>F</b>) β-gal staining of a coronal section through the first mandibular arch. <b>F</b> is a magnified section of the boxed area shown in <b>E</b>.</div>
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<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4b/3613930/baa9ab0e449b/JCI66903.f2.gif"
alt="Figure 2" />
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<p> Figure 2. Ca <sub> V </sub> 1.2 expression in… </p>
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<strong class="figure-label">
<p> Figure 2. Ca <sub> V </sub> 1.2 expression in pharyngeal arches affects craniofacial development. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) X-rays of… </p></div>
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<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2. Ca<sub>V</sub>1.2 expression in pharyngeal arches affects craniofacial development.
</strong>
<div class="figure-caption-contents">(<b>A</b>) X-rays of a <i>Prx-Ca<sub>V</sub>1.2<sup>WT</sup></i> skull and a <i>Prx1<sup></sup></i> littermate skull. Note that the upper jaw extends anteriorly to the mandible (arrows). (<b>B</b>) X-rays of a <i>Prx1-Ca<sub>V</sub>1.2<sup>TS</sup></i> skull and a <i>Prx1<sup></sup></i> littermate skull. When Ca<sub>V</sub>1.2<sup>TS</sup> is expressed (in the <i>Prx1<sup>+</sup></i> animal), the mandible extends more anteriorly, as is also seen in TS patients. (<b>C</b>) Image showing patient phenotype (arrow points to mandible). Image in <b>C </b>is reproduced with permission from the authors and publisher (1). (<b>D</b>) Mandibles from adult <i>Ca<sub>V</sub>1.2<sup>+/LacZ</sup></i> or wild-type (littermates). Note reduced width between coronoid processes in <i>Ca<sub>V</sub>1.2<sup>+/LacZ</sup></i> compared with wild-type mice. Scale bars: 5 mm.</div>
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data-image-width="730"
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<p> Figure 3. Ca <sup> 2+ </sup> influx through Ca… </p>
</strong>
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<strong class="figure-label">
<p> Figure 3. Ca <sup> 2+ </sup> influx through Ca <sub> V </sub> 1.2 regulates size of mandible in zebrafish. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> )… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3. Ca<sup>2+</sup> influx through Ca<sub>V</sub>1.2 regulates size of mandible in zebrafish.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Alcian bluestained embryos at 72 hpf. CON, uninjected control; CMO, control morpholino; MO, Ca<sub>V</sub>1.2 morpholinos; MO + WT, Ca<sub>V</sub>1.2 morpholinos coinjected with rabbit Ca<sub>V</sub>1.2<sup>WT</sup> cRNA; MO + 4EQ, Ca<sub>V</sub>1.2 morpholinos coinjected with rabbit Ca<sub>V</sub>1.2 cRNA with mutations in the 4-pore glutamates (non-Ca<sup>2+</sup> permeant); MO + TS, Ca<sub>V</sub>1.2 morpholinos coinjected with rabbit Ca<sub>V</sub>1.2<sup>TS</sup> cRNA. (<b>B</b>) Mandibular area (as outlined for CON in <b>A</b> normalized to the area in CMO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus CMO. (<b>C</b>) Mandibular area normalized to the area in MO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus MO. (<b>D</b>) Alcian bluestained embryos at 72 hpf after treatment with DMSO or nisoldipine. (<b>E</b>) Mandibular area normalized to the area in DMSO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus DMSO.</div>
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data-image-width="744"
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Figure 4. Ca <sup> 2+ </sup> influx through Ca… </p>
</strong>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4. Ca <sup> 2+ </sup> influx through Ca <sub> V </sub> 1.2 affects cellular hypertrophy and hyperplasia in… </p>
</strong>
<div class="figure-caption-contents"><p> (… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4. Ca<sup>2+</sup> influx through Ca<sub>V</sub>1.2 affects cellular hypertrophy and hyperplasia in the mandible.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Low-power DIC image of flat-mounted, Alcian bluestained CON embryo. The red box indicates the region from which images in <b>B</b>, <b>D</b>, and <b>F</b> were obtained. (<b>B</b>) Higher magnification of the region shown in <b>A</b> for an embryo treated with DMSO or NIS. (<b>C</b>) Cell size normalized to DMSO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus DMSO. (<b>D</b>) Higher magnification of the region shown in <b>A</b> for a CON, CMO, or MO embryo. (<b>E</b>) Cell size normalized to CMO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus CMO. (<b>F</b>) Higher magnification of the region shown in <b>A</b> for an MO + WT, MO + TS, or MO + 4EQ embryo. (<b>G</b>) Cell size normalized to MO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus MO; **<i>P</i> &lt; 0.001 versus MO + WT or versus MO. (<b>H</b>) BrdU staining and quantification of BrdU<sup>+</sup> cells (in GFP<sup>+</sup> cells) of <i>sox10<sup>+</sup></i> zebrafish embryos treated with CMO or MO. *<i>P</i> &lt; 0.001. Note that we were unable to use 1-phenyl 2-thiourea, the tyrosinase inhibitor commonly used to block pigmentation and aid visualization (for BrdU staining) in zebrafish because it interferes with neural crest development (32): the larger red nuclei likely denote newly produced melanocytes, which migrate to the same area, and were not counted.</div>
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<p> Figure 5. Calcineurin, downstream of Ca <sub> V… </sub> </p>
</strong>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5. Calcineurin, downstream of Ca <sub> V </sub> 1.2, regulates cellular hypertrophy in the developing mandible. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A… </b> </p></div>
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<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5. Calcineurin, downstream of Ca<sub>V</sub>1.2, regulates cellular hypertrophy in the developing mandible.
</strong>
<div class="figure-caption-contents">(<b>A</b>) Alcian bluestained embryo treated with DMSO or a combination of cyclosporine and FK506 (FK/CsA). (<b>B</b>) Mandibular area normalized to the area in DMSO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus DMSO. (<b>C</b>) Alcian bluestained embryo treated with MO or MO plus cRNA for a constitutively active calcineurin (MO + caCN). (<b>D</b>) Mandibular area normalized to the area in MO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus MO. (<b>E</b>) Higher magnification of the region shown in Figure 4A for an embryo treated with DMSO or FK/CsA. (<b>F</b>) Cell size normalized to DMSO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus DMSO. (<b>G</b>) Higher magnification of the region shown in Figure 4A for an embryo treated with MO or MO + caCN. (<b>H</b>) Cell size normalized to MO (<i>n</i> = 20 for each). *<i>P</i> &lt; 0.001 versus MO. Scale bar: 200 μm.</div>
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<p> Figure 6. <i> sox10 <sup> + </sup> </i> cranial neural crestderived… </p>
</strong>
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<strong class="figure-label">
<p> Figure 6. <i> sox10 <sup> + </sup> </i> cranial neural crestderived cells express functional Ca <sub> V </sub> 1.2 channels. </p>
</strong>
<div class="figure-caption-contents"><p> ( <b> A </b> ) GFP… </p></div>
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<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6. <i>sox10<sup>+</sup></i> cranial neural crestderived cells express functional Ca<sub>V</sub>1.2 channels.
</strong>
<div class="figure-caption-contents">(<b>A</b>) GFP images of decapitated <i>sox10-GFP</i> transgenic embryos at approximately 65 hpf of a control or Ca<sub>V</sub>1.2 MO embryo. Arrowhead denotes migrating cranial neural crest. (<b>B</b>) Sample GFP<sup>+</sup> cell after single-cell isolation. Image on the right shows a DAPI overlay. Note the GFP<sup></sup> cell. (<b>C</b>) Whole-cell Ca<sup>2+</sup> current from a GFP<sup>+</sup> cell isolated from an MO or CON embryo. Voltage ramp protocol shown below. (<b>D</b>) Box plot showing current density for MO or CON embryos. *<i>P</i> &lt; 0.01. Scale bar: 5 μm.</div>
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<div id="substances" class="substances keywords-section">
<h2 class="title">
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Supplementary concepts
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