Epistatic and independent functions of caspase-3 and Bcl-X(L) in developmental programmed cell death.
Proc Natl Acad Sci U S A
; 97(1): 466-71, 2000 Jan 04.
Article
en En
| MEDLINE
| ID: mdl-10618441
ABSTRACT
The number of neurons in the mammalian brain is determined by a balance between cell proliferation and programmed cell death. Recent studies indicated that Bcl-X(L) prevents, whereas Caspase-3 mediates, cell death in the developing nervous system, but whether Bcl-X(L) directly blocks the apoptotic function of Caspase-3 in vivo is not known. To examine this question, we generated bcl-x/caspase-3 double mutants and found that caspase-3 deficiency abrogated the increased apoptosis of postmitotic neurons but not the increased hematopoietic cell death and embryonic lethality caused by the bcl-x mutation. In contrast, caspase-3, but not bcl-x, deficiency changed the normal incidence of neuronal progenitor cell apoptosis, consistent with the lack of expression of Bcl-X(L) in the proliferative population of the embryonic cortex. Thus, although Caspase-3 is epistatically downstream to Bcl-X(L) in postmitotic neurons, it independently regulates apoptosis of neuronal founder cells. Taken together, these results establish a role of programmed cell death in regulating the size of progenitor population in the central nervous system, a function that is distinct from the classic role of cell death in matching postmitotic neuronal population with postsynaptic targets.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apoptosis
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Regulación del Desarrollo de la Expresión Génica
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Proteínas Proto-Oncogénicas c-bcl-2
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Caspasas
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Sistema Nervioso
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos