Neurotrophin-3 in the development of the enteric nervous system

被引:56
作者
Chalazonitis, A [1 ]
机构
[1] Columbia Univ Teachers Coll, Dept Anat & Cell Biol, New York, NY 10032 USA
来源
NGF AND RELATED MOLECULES IN HEALTH AND DISEASE | 2004年 / 146卷
关键词
neural crest; immunoselection; NT-3; TrkC; GDNF; neuropoietic cytokines; bone morphogenetic proteins; noggin; transgenic mice; gut;
D O I
10.1016/S0079-6123(03)46016-0
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To date, the only neurotrophin that has been shown to influence the development of the enteric nervous system (ENS) is neurotrophin-3 (NT-3). NT-3 plays an essential role in the development of both the neural-crest-derived peripheral nervous system and the central nervous system (i.e., Chalazonitis, 1996, Mol. Neurobiol., 12: 39-53; Sieber-Blum, 1999, Neurotrophins and the Neural Crest, CRC Press, Boca Raton). This review integrates data obtained from our laboratory and from our collaboration with other investigators that demonstrate a late-acting role for NT-3 in the development of enteric neurons in vitro and in vivo. Studies of the biological actions of NT-3 on enteric neuronal precursors in vitro demonstrate that NT-3 acts directly on the precursor cells and that it also acts in combination with other neurotrophic factors such as glial cell line-derived neurotrophic factor and a ciliary neurotrophic factor-like molecule, to promote the survival and differentiation of enteric neurons and glia. Importantly, bone morphogenetic protein-2 (BMP-2) and BMP-4, members of the transforming growth factor-beta (TGF-beta) superfamily, regulate the onset of action of NT-3 during fetal gut development. Analyzes performed on mice deficient in the genes encoding NT-3 or its transducing tyrosine kinase receptor, TrkC, and conversely on transgenic mice that overexpress NT-3 substantiate a physiological role for NT-3 in the development and maintenance of a subset of enteric neurons. There is loss of neurons in both the myenteric and submucosal plexuses of mice lacking NT-3/TrkC signaling and selective hyperplasia in the myenteric plexus of mice overexpressing NT-3. Analyzes performed on transgenic mice that overexpress noggin, a specific BMP-4 antagonist, show significant decreases in the density of TrkC-expressing neurons but significant increase in overall neuronal density of both plexuses. Conversely, overexpression of BMP-4 is sufficient to produce, an increase in the proportion of TrkC-expressing neurons in both plexuses. Overall, our data point to a regulatory role of BMP-4 in the responses of subsets of myenteric and submucosal neurons to NT-3. NT-3 is required for the differentiation, maintenance and proper physiological function of late-developing enteric neurons that are important for the control of gut peristalsis.
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收藏
页码:243 / 263
页数:21
相关论文
共 121 条
[1]   Human GFRA1:: Cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility [J].
Angrist, M ;
Jing, SQ ;
Bolk, S ;
Bentley, K ;
Nallasamy, S ;
Halushka, M ;
Fox, GM ;
Chakravarti, A .
GENOMICS, 1998, 48 (03) :354-362
[2]   TRANSIENT CATECHOLAMINERGIC (TC) CELLS IN THE VAGUS NERVES AND BOWEL OF FETAL MICE - RELATIONSHIP TO THE DEVELOPMENT OF ENTERIC NEURONS [J].
BAETGE, G ;
GERSHON, MD .
DEVELOPMENTAL BIOLOGY, 1989, 132 (01) :189-211
[3]   TRANSIENTLY CATECHOLAMINERGIC (TC) CELLS IN THE BOWEL OF THE FETAL-RAT - PRECURSORS OF NONCATECHOLAMINERGIC ENTERIC NEURONS [J].
BAETGE, G ;
PINTAR, JE ;
GERSHON, MD .
DEVELOPMENTAL BIOLOGY, 1990, 141 (02) :353-380
[4]   Glial-derived neurotrophic factor in human adult and fetal intestine and in Hirschsprung's disease [J].
Bar, KJ ;
Facer, P ;
Williams, NS ;
Tam, PKH ;
Anand, P .
GASTROENTEROLOGY, 1997, 112 (04) :1381-1385
[5]   INTERACTION OF ENDOTHELIN-3 WITH ENDOTHELIN-B RECEPTOR IS ESSENTIAL FOR DEVELOPMENT OF EPIDERMAL MELANOCYTES AND ENTERIC NEURONS [J].
BAYNASH, AG ;
HOSODA, K ;
GIAID, A ;
RICHARDSON, JA ;
EMOTO, N ;
HAMMER, RE ;
YANAGISAWA, M .
CELL, 1994, 79 (07) :1277-1285
[6]  
Blaugrund E, 1996, DEVELOPMENT, V122, P309
[7]  
BRAZEAU P, 1981, REGUL PEPTIDES, V1, P225
[8]   p75(NTR) and apoptosis: Trk-dependent and Trk-independent effects [J].
Bredesen, DE ;
Rabizadeh, S .
TRENDS IN NEUROSCIENCES, 1997, 20 (07) :287-290
[9]   Neuregulin and ErbB receptor signaling pathways in the nervous system [J].
Buonanno, A ;
Fischbach, GD .
CURRENT OPINION IN NEUROBIOLOGY, 2001, 11 (03) :287-296
[10]  
Burns AJ, 1998, DEVELOPMENT, V125, P4335