Neural stem cell self-renewal requires the Mrj co-chaperone.
The Mrj co-chaperone is expressed throughout the mouse conceptus, yet its requirement for placental development has prohibited a full understanding of its embryonic function. Here, we show that Mrj(-/-) embryos exhibit neural tube defects independent of the placenta phenotype, including exencephaly and thin-walled neural tubes. Molecular analyses revealed fewer proliferating cells and a down-regulation of early neural progenitor (Pax6, Olig2, Hes5) and neuronal (Nscl2, SCG10) cell markers in Mrj(-/-) neuroepithelial cells. Furthermore, Mrj(-/-) neurospheres are significantly smaller and form fewer secondary neurospheres indicating that Mrj is necessary for self-renewal of neural stem cells. However, the molecular function of Mrj in this context remains elusive because Mrj does not colocalize with Bmi-1, a self-renewal protein. Furthermore, unlike in Mrj(-/-) placentas, intermediate filament-containing aggregates do not accumulate in Mrj(-/-) neuroepithelium, ruling out nestin as a substrate for Mrj. Regardless, Mrj plays an important role in neural stem cell self-renewal.
Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.
Erica D
ED
Watson
Pierre
P
Mattar
Carol
C
Schuurmans
James C
JC
Cross
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000033:anatomy & histology / Q000502:physiology; D004848:Epithelium / Q000033:anatomy & histology / Q000502:physiology; D005865:Gestational Age; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D054259:Neural Tube / Q000033:anatomy & histology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
D015415:Biomarkers; C489421:Bmi1 protein, mouse; C118476:Dnajb6 protein, mouse; D050956:HSP40 Heat-Shock Proteins; D007381:Intermediate Filament Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1