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PLoS One. January 1, 2011; 6 (6): e20309.

Yes-associated protein 65 (YAP) expands neural progenitors and regulates Pax3 expression in the neural plate border zone.

Gee ST , Milgram SL , Kramer KL , Conlon FL , Moody SA .

Yes-associated protein 65 (YAP) contains multiple protein-protein interaction domains and functions as both a transcriptional co-activator and as a scaffolding protein. Mouse embryos lacking YAP did not survive past embryonic day 8.5 and showed signs of defective yolk sac vasculogenesis, chorioallantoic fusion, and anterior-posterior (A-P) axis elongation. Given that the YAP knockout mouse defects might be due in part to nutritional deficiencies, we sought to better characterize a role for YAP during early development using embryos that develop externally. YAP morpholino (MO)-mediated loss-of-function in both frog and fish resulted in incomplete epiboly at gastrulation and impaired axis formation, similar to the mouse phenotype. In frog, germ layer specific genes were expressed, but they were temporally delayed. YAP MO-mediated partial knockdown in frog allowed a shortened axis to form. YAP gain-of-function in Xenopus expanded the progenitor populations in the neural plate (sox2(+)) and neural plate border zone (pax3(+)), while inhibiting the expression of later markers of tissues derived from the neural plate border zone (neural crest, pre-placodal ectoderm, hatching gland), as well as epidermis and somitic muscle. YAP directly regulates pax3 expression via association with TEAD1 (N-TEF) at a highly conserved, previously undescribed, TEAD-binding site within the 5'' regulatory region of pax3. Structure/function analyses revealed that the PDZ-binding motif of YAP contributes to the inhibition of epidermal and somitic muscle differentiation, but a complete, intact YAP protein is required for expansion of the neural plate and neural plate border zone progenitor pools. These results provide a thorough analysis of YAP mediated gene expression changes in loss- and gain-of-function experiments. Furthermore, this is the first report to use YAP structure-function analyzes to determine which portion of YAP is involved in specific gene expression changes and the first to show direct in vivo evidence of YAP''s role in regulating pax3 neural crest expression.

PubMed ID: 21687713
PMC ID: PMC3110623
Article link: PLoS One.
Grant support: HL-65755 NHLBI NIH HHS , R01 DE018825 NIDCR NIH HHS, R01 HL089641 NHLBI NIH HHS , Intramural NIH HHS, Intramural NIH HHS, R01 HL089641 NHLBI NIH HHS , R01 HL065755 NHLBI NIH HHS , R01 DE018825 NIDCR NIH HHS, HL-65755 NHLBI NIH HHS

Genes referenced: cdknx chrd.1 eomes foxd3 gal.2 gsc hes1 hnrnpc myod1 neurod1 nodal nodal3.1 notch1 pax3 sia1 six1 sox11 sox17a sox2 t tead1 tef tubb2b ventx2.2 wnt8a yap1 yes1 zic1 not

Antibodies referenced: Eef2.1 Ab1 Yap1 Ab1
Morpholinos referenced: yap1 MO1 yap1 MO2 yap1 MO3 yap1 MO4 yap1 MO5

Bork, 1995, Pubmed[+]

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