The mesenchyme controls the timing of pancreatic β-cell differentiation

被引:79
作者
Duvillié, B
Attali, M
Bounacer, A
Ravassard, P
Basmaciogullari, A
Scharfmann, R
机构
[1] Univ Paris Descartes, Fac Med, Hop Necker, INSERM,E363, Paris, France
[2] Hop La Pitie Salpetriere, CNRS, UMR7091, Paris, France
关键词
D O I
10.2337/diabetes.55.03.06.db05-0839
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The importance of mesenchymal-epithelial interactions in the proliferation of pancreatic progenitor cells is well established. Here, we provide evidence that the mesenchyme also controls the timing of beta-cell differentiation. When rat embryonic pancreatic epithelium was cultured without mesenchyme, we found first rapid induction in epithelial progenitor cells of the transcription factor nertrogenin3 (Ngn3), a master gene controlling endocrine cell-fate decisions in progenitor cells; then beta-cell differentiation occurred. In the presence of mesenchyme, Ngn3 induction was delayed, and few beta-cells developed. This effect of the mesenchyme on Ngn3 induction was mediated by cell-cell contacts and required a functional Notch pathway. We then showed that associating Ngn3-expressing epithelial cells with mesenchyme resulted in poor beta-cell development via a mechanism mediated by soluble factors. Thus, in addition to its effect upstream of Ngn3, the mesenchyme regulated beta-cell differentiation downstream of Ngn3. In conclusion, these data indicate that the mesenchyme controls the timing of beta-cell differentiation both upstream and downstream of Ngn3.
引用
收藏
页码:582 / 589
页数:8
相关论文
共 41 条
[1]  
Ahlgren U, 1996, DEVELOPMENT, V122, P1409
[2]   Notch signalling controls pancreatic cell differentiation [J].
Apelqvist, Å ;
Li, H ;
Sommer, L ;
Beatus, P ;
Anderson, DJ ;
Honjo, T ;
de Angelis, MH ;
Lendahl, U ;
Edlund, H .
NATURE, 1999, 400 (6747) :877-881
[3]  
Bhushan A, 2001, DEVELOPMENT, V128, P5109
[4]   Differentiation of pluripotent embryonic stem cells into cardiomyocytes [J].
Boheler, KR ;
Czyz, J ;
Tweedie, D ;
Yang, HT ;
Anisimov, SV ;
Wobus, AM .
CIRCULATION RESEARCH, 2002, 91 (03) :189-201
[5]   γ-Secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney [J].
Cheng, HT ;
Miner, JH ;
Lin, MH ;
Tansey, MG ;
Roth, K ;
Kopan, R .
DEVELOPMENT, 2003, 130 (20) :5031-5042
[6]  
CONLON RA, 1995, DEVELOPMENT, V121, P1533
[7]   Epidermal growth factor increases undifferentiated pancreatic embryonic cells in vitro -: A balance between proliferation and differentiation [J].
Cras-Méneur, C ;
Elghazi, L ;
Czernichow, P ;
Scharfmann, R .
DIABETES, 2001, 50 (07) :1571-1579
[8]   Label-retaining cells in the rat pancreas -: Location and diferentiation potential in vitro [J].
Duvillié, B ;
Attali, M ;
Aiello, V ;
Quemeneur, E ;
Scharfmann, R .
DIABETES, 2003, 52 (08) :2035-2042
[9]   Transcribing pancreas [J].
Edlund, H .
DIABETES, 1998, 47 (12) :1817-1823
[10]   Role for FGFR2IIIb-mediated signals in controlling pancreatic endocrine progenitor cell proliferation [J].
Elghazi, L ;
Cras-Méneur, C ;
Czernichow, P ;
Scharfmann, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (06) :3884-3889