Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70.
Neuronal cell death is a genuine developmental process, with precise regulation and defined roles. In striking contrast, characterization of cell death that occurs at early stages of neural development is very limited. We previously showed that embryonic proinsulin increases the level of the chaperone heat shock cognate 70 (Hsc70) and reduces the incidence of apoptosis in the neurulating chick embryo [de la Rosa, et al. (1998), Proc. Natl. Acad. Sci. USA, 95, 9950]. We now demonstrate that Hsc70 is directly involved in cell survival during neurulation, as specific downregulation of endogenous Hsc70 by antisense oligodeoxynucleotide interference provoked an increase in apoptosis both in vitro and in ovo. In parallel, activation of caspase-3 was increased after hsc70 antisense oligodeoxynucleotide treatment. Dead cells were located mostly in the developing nervous system, distributed in areas where the incidence of cell death was high. These areas coincided both in vivo and under different death-inducing conditions, including antisense interference and growth factor deprivation. Hsc70 immunostaining was strong in at least some areas of high cell death. Apoptotic cells within these areas presented undetectable Hsc70 levels, however, suggesting that this protein acts as an intrinsic protector of neuroepithelial and neural precursor cells.
Rubio
Eva
E
Group of Growth Factors in Vertebrate Development, Department of Cell and Developmental Biology, Centro de Investigaciones Biológicas, CSIC, Velázquez 144, E-28006 Madrid, Spain.
Valenciano
Ana I
AI
Segundo
Carmen
C
Sánchez
Noelia
N
de Pablo
Flora
F
de la Rosa
Enrique J
EJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002642:Chick Embryo / Q000502:physiology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology
D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D053148:Caspase 3; D020169:Caspases