Apoptosis in the Medaka Embryo in the Early Developmental Stage

Apoptosis is an important event of the development of various organs. In this study, we used in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) to visualize the temporal and spatial distribution of apoptosis in the developing medaka embryo, which is a useful model for developmental biology and genetics. Most of the apoptotic cells were distributed in the central nervous system and tailbud. In the brain and retina, most of the apoptosis occurred in the restricted period. In situ hybridization against caspase 3A and caspase 3B showed that these were distributed in the tailbud and the head, respectively. These results suggested that two types of caspase 3 were involved in apoptosis in different areas

ERK Regulates Renal Cell Proliferation and Renal Cyst Expansion in inv Mutant Mice

Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage kidney disease in children and young adults. Inv mice are a model for human nephronophthisis type 2 (NPHP2) and characterized by multiple renal cysts and situs inversus. Renal epithelial cells in inv cystic kidneys show increased cell proliferation. We studied the ERK pathway to understand the mechanisms that induce cell proliferation and renal cyst progression in inv kidneys. We studied the effects of ERK suppression by administering PD184352, an oral mitogen-activated protein kinase kinase (MEK) inhibitor on renal cyst expansion, extracellular signal-regulated protein kinase (ERK) activity, bromo-deoxyuridine (BrdU) incorporation and expression of cell-cycle regulators in invΔC kidneys. Phosphorylated ERK (p-ERK) level increased along with renal cyst enlargement. Cell-cycle regulators showed a high level of expression in invΔC kidneys. PD184352 successfully decreased p-ERK level and inhibited renal cyst enlargement. The inhibitor also decreased expression of cell-cycle regulators and BrdU incorporation in renal epithelial cells. The present results showed that ERK regulated renal cell proliferation and cyst expansion in inv mutants