What do knockout models teach us about the enteric nervous system?
Since the first histological studies, enormous strides have been made in understanding the genetics and cell biology of enteric nervous system (ENS) formation. Several mitogenic and trophic factors have been implicated in the process of neural cell proliferation and differentiation. A number of natural (piebald-lethal mice [s l], lethal spotting mice [ls], spotting lethal rats [sl]) or target (Gfralpha1-deficient mice, ret.k - mice, and NT-4 knockout mice) mutations have been reported to produce developmental defects in neural crest cell migration, differentiation or survival. Study of these mutations continues to provide new insights into this complex system. In the present investigation, we showed that a lack of basic fibroblast growth factor (FGF) or growth hormone (GH) leads to morphological abnormalities of the enteric nervous system. Because knockouts, neither of FGF nor of GH, produce enteric nervous system defects substantial enough to compromise the ability of the gut to support life, we postulate that FGF and GH affect only a relatively small subset of neurons and/or that compensatory effects of other growth factors might occur.
Hagl
C I
CI
Department of Paediatric Surgery, Clinical Hospital Mannheim, University Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany. cornelia.hagl@kch.ma.uni-heidelberg.de
Holland-Cunz
S
S
Schäfer
K-H
KH
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000254:growth & development / Q000648:ultrastructure; D016222:Fibroblast Growth Factor 2 / Q000172:deficiency / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006627:Hirschsprung Disease / Q000235:genetics* / Q000378:metabolism; D019382:Human Growth Hormone / Q000172:deficiency / Q000378:metabolism; D007410:Intestinal Diseases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism; D015398:Signal Transduction
C495040:Gdnf protein, mouse; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017466:Receptors, Endothelin; D016222:Fibroblast Growth Factor 2; D019382:Human Growth Hormone; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C494999:Ret protein, mouse