Hes1-deficient mice show precocious differentiation of Paneth cells in the small intestine.
We have previously shown that Hes1 is expressed both in putative epithelial stem cells just above Paneth cells and in the crypt base columnar cells between Paneth cells, while Hes1 is completely absent in Paneth cells. This study was undertaken to clarify the role of Hes1 in Paneth cell differentiation, using Hes1-knockout (KO) newborn (P0) mice. Electron microscopy revealed premature appearance of distinct cells containing cytoplasmic granules in the intervillous region in Hes1-KO P0 mice, whereas those cells were absent in wild-type (WT) P0 mice. In Hes1-KO P0 mice, the gene expressions of cryptdins, exclusively present in Paneth cells, were all enhanced compared with WT P0 mice. Immunohistochemistry demonstrated increased number of both lysozyme-positive and cryptdin-4-positive cells in the small intestinal epithelium of Hes1-KO P0 mice as compared to WT P0 mice. Thus, Hes1 appears to have an inhibitory role in Paneth cell differentiation in the small intestine.
Suzuki
Katsumasa
K
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Fukui
Hirokazu
H
Kayahara
Takahisa
T
Sawada
Mitsutaka
M
Seno
Hiroshi
H
Hiai
Hiroshi
H
Kageyama
Ryoichiro
R
Okano
Hideyuki
H
Chiba
Tsutomu
T
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009113:Muramidase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019879:Paneth Cells / Q000166:cytology* / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D023084:alpha-Defensins / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009113:Muramidase; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D016601:RNA-Binding Proteins; D000072056:Transcription Factor HES-1; D023084:alpha-Defensins; C489734:Hes1 protein, mouse; C104786:Msi1h protein, mouse; C401847:cryptdin 4, mouse; C059569:cryptdin