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Stem Cells November 1, 2010; 28 (11): 1950-60.
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Neuronatin promotes neural lineage in ESCs via Ca(2+) signaling.

Lin HH , Bell E , Uwanogho D , Perfect LW , Noristani H , Bates TJ , Snetkov V , Price J , Sun YM .

Neural induction is the first step in the formation of the vertebrate central nervous system. The emerging consensus of the mechanisms underlying neural induction is the combined influences from inhibiting bone morphogenetic protein (BMP) signaling and activating fibroblast growth factor (FGF)/Erk signaling, which act extrinsically via either autocrine or paracrine fashions. However, do intrinsic forces (cues) exist and do they play decisive roles in neural induction? These questions remain to be answered. Here, we have identified a novel neural initiator, neuronatin (Nnat), which acts as an intrinsic factor to promote neural fate in mammals and Xenopus. ESCs lacking this intrinsic factor fail to undergo neural induction despite the inhibition of the BMP pathway. We show that Nnat initiates neural induction in ESCs through increasing intracellular Ca(2+) ([Ca(2+) ](i)) by antagonizing Ca(2+) -ATPase isoform 2 (sarco/endoplasmic reticulum Ca(2+) -ATPase isoform 2) in the endoplasmic reticulum, which in turn increases the phosphorylation of Erk1/2 and inhibits the BMP4 pathway and leads to neural induction in conjunction with FGF/Erk pathway.

PubMed ID: 20872847
PMC ID: PMC3003906
Article link: Stem Cells
Grant support: [+]

Species referenced: Xenopus
Genes referenced: atp2a2 bag3 bmp4 chrd.1 fgf4 fst hnf4a krt18.1 map2 mapk1 mespb msx1 msx2 ncam1 nkx2-5 nog nrp1 odc1 otx2 pax6 pou5f3.1 rbfox3 six3 smad1 sox1 tbxt

Article Images: [+] show captions
References [+] :
Aubert, Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation. 2002, Pubmed