Early acquisition of bowel segment-specific Bcl-2 homolog expression profiles during development of the human ileum and colon.
The adult small and large intestines display distinct expression profiles of Bcl-2 homologs, known regulators of apoptosis. This is thought to indicate that control mechanisms of intestinal apoptosis are gut segment-specific. Little is known on the expression of Bcl-2 homologs during gut development. In man, intestinal features and functions are acquired largely by mid-gestation (18-20 wks); the question whether segment-specific controls of intestinal apoptosis are also acquired early during development remains open. In the present study, we approached this by investigating the expression of six Bcl-2 homologs (Bcl-2, Bcl-XL, Mcl-1, Bax, Bak, Bad), and one nonhomologous associated molecule (Bag-1), during development of the human ileum and colon (12-20 wks of gestation). Beginning at 18 wks, we found that the epithelial localization of Bcl-2 homologs displayed differential patterns (or gradients) in both the ileum and colon; however, the patterns of some of the homologs differed between the two segments. For instance, Bag-1 and Bcl-2 exhibited crypt-villus decreasing gradients of expression in the ileum but not in the colon, whereas Mcl-1 displayed differing compartimentalizations between the two segments. Further analyses indicated that the steady-state expression levels of Bcl-2 homologs underwent modulations between 12 and 20 wks; however, the observed developmental profiles contrasted significantly between the two segments. For example, Bcl-2, Bag-1 and Bak levels increased in the colon, but the levels of these same homologs decreased in the ileum. Furthermore, by 18-20 wks, we found that the expression levels of each Bcl-2 homolog analyzed differed greatly between the ileum and colon. Altogether, these data indicate that the expression of Bcl-2 homologs is modulated differentially during human gut development in order to establish, by mid-gestation, distinct expression profiles for the small and large intestines. This in turn suggests that gut segment-specific control mechanisms of human intestinal apoptosis are acquired early during fetal life.
Vachon
P H
PH
Department of Anatomy and Cell Biology, Faculty of Medicine, University of Sherbrooke, QC, Canada. phvachon@courrier.usherb.ca
Cardin
E
E
Harnois
C
C
Reed
J C
JC
Plourde
A
A
Vézina
A
A
D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000196:embryology* / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D007082:Ileum / Q000196:embryology* / Q000378:metabolism*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C494819:BAD protein, human; C494772:BAK1 protein, human; C494826:BAX protein, human; C091732:BCL2-associated athanogene 1 protein; C494811:BCL2L1 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein