TY  - JOUR
A1  - Schwartz, Faina
A1  - Neve, Rachel
A1  - Eisenman, Robert
A1  - Gessler, Manfred
A1  - Bruns, Gail
T1  - A WAGR region gene between PAX-6 and FSHB expressed in fetal brain
N2  - Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11 p 13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as weil as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development.
KW  - Biochemie
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59125
ER  - 
TY  - JOUR
A1  - Scognamiglio, Roberta
A1  - Cabezas-Wallscheid, Nina
A1  - Thier, Marc Christian
A1  - Altamura, Sandro
A1  - Reyes, Alejandro
A1  - Prendergast, Áine M.
A1  - Baumgärtner, Daniel
A1  - Carnevalli, Larissa S.
A1  - Atzberger, Ann
A1  - Haas, Simon
A1  - von Paleske, Lisa
A1  - Boroviak, Thorsten
A1  - Wörsdörfer, Philipp
A1  - Essers, Marieke A. G.
A1  - Kloz, Ulrich
A1  - Eisenman, Robert N.
A1  - Edenhofer, Frank
A1  - Bertone, Paul
A1  - Huber, Wolfgang
A1  - van der Hoeven, Franciscus
A1  - Smith, Austin
A1  - Trumpp, Andreas
T1  - Myc depletion induces a pluripotent dormant state mimicking diapause
JF  - Cell
N2  - Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.
KW  - hematopoietic stem cells
KW  - leukemia inhibitory factor
KW  - c-Myc
KW  - N-Myc
KW  - gene expression
KW  - embryonic stem cells
KW  - self-renewal
KW  - protein synthesis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190868
VL  - 164
IS  - 4
ER  -