Strain-specific caspase-3-dependent programmed cell death in the early developing mouse forebrain.
Caspase-3-deficient 129/Sv mice show hyperplasia of the forebrain at embryonic day (E) 10.5, which suggests that caspase-3-dependent programmed cell death (PCD) plays an essential role in brain morphogenesis prior to neurogenesis. However, little is known about region-specific caspase-3-dependent PCD in the developing forebrain. We examined the PCD region in the early developmental brain at E9.5 by whole mount terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). In addition to hindbrain, TUNEL-reactivity was detected in the ventral forebrain and in the caudal portion of the front nasal region, just behind the regions expressing fgf-8 and otx-2. It has been shown recently that brain hyperplasia induced by caspase-3-deficiency is mouse strain-dependent; such that brain abnormalities were observed in caspase-3-deficient 129/Sv mice but not in caspase-3-deficient C57BL/6 mice. We examined the caspase-3-dependent PCD in the ventral forebrain of 129/Sv and C57BL/6 mouse embryos (E8.5-9 and E9.5) by double staining of TUNEL and antiserum against the active form of caspase-3 (anti-m3D175). TUNEL/anti-m3D175 reactivity in the ventral forebrain was mouse strain-dependent, such that many TUNEL/anti-m3D175-positive cells were detected in the ventral forebrains of 129/Sv mice, but were not observed in C57BL/6 mice. Thus, it is likely that this region is the site of the strain-specific caspase-3-dependent PCD. A strain-dependent 'modulator' that regulates both caspase-3-dependent and -independent cell death pathways may control PCD in the ventral forebrain at E8.5-9.5.
Momoi
Takashi
T
Division of Developmental Differentiation, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan. momoi@ncnp.go.jp
Fujita
Eriko
E
Urase
Koko
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D053148:Caspase 3; D020169:Caspases / Q000172:deficiency / Q000502:physiology*; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000032:analysis; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000032:analysis; D006965:Hyperplasia; D020287:In Situ Nick-End Labeling; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains / Q000196:embryology / Q000502:physiology*; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000032:analysis; D051857:Otx Transcription Factors; D016548:Prosencephalon / Q000737:chemistry / Q000166:cytology* / Q000196:embryology / Q000473:pathology; D011506:Proteins / Q000032:analysis; D013045:Species Specificity; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis
D015415:Biomarkers; C501127:Dkk1 protein, mouse; C496457:Fgf8 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D011506:Proteins; C465570:Shh protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases