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Cell Rep 2015 Oct 27;134:829-839. doi: 10.1016/j.celrep.2015.09.035.
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T-type Calcium Channel Regulation of Neural Tube Closure and EphrinA/EPHA Expression.

Abdul-Wajid S , Morales-Diaz H , Khairallah SM , Smith WC .

A major class of human birth defects arise from aberrations during neural tube closure (NTC). We report on a NTC signaling pathway requiring T-type calcium channels (TTCCs) that is conserved between primitive chordates (Ciona) and Xenopus. With loss of TTCCs, there is a failure to seal the anterior neural folds. Accompanying loss of TTCCs is an upregulation of EphrinA effectors. Ephrin signaling is known to be important in NTC, and ephrins can affect both cell adhesion and repulsion. In Ciona, ephrinA-d expression is downregulated at the end of neurulation, whereas, with loss of TTCC, ephrinA-d remains elevated. Accordingly, overexpression of ephrinA-d phenocopied TTCC loss of function, while overexpression of a dominant-negative Ephrin receptor was able to rescue NTC in a Ciona TTCC mutant. We hypothesize that signaling through TTCCs is necessary for proper anterior NTC through downregulation of ephrins, and possibly elimination of a repulsive signal.

PubMed ID: 26489462
PMC ID: PMC4980084
Article link: Cell Rep
Grant support: [+]

Species referenced: Xenopus
Genes referenced: acta4 cacna1h cav3.1 cdh1 celf3 epha2 h2bc21 h4c3 ncam1 rps27a ubb
Morpholinos: cacna1h MO1 cacna1h MO2

Phenotypes: Xla Wt + cacna1h MO (Fig 3. D) [+]

Article Images: [+] show captions
References [+] :
Abdul-Aziz, EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion. 2009, Pubmed