Kyoto University · 생화학·유전·분자생물학
Ryoichiro Kageyama 교수의 연구실은 신경계 발달과 체세포 분화 조절을 중심으로, Hes 유전자 가족이 조절하는 세포 결정 및 분화 시계 메커니즘을 연구하고 있습니다. 특히 Notch 신호전달 경로와 연관된 Hes 유전자들이 신경줄기세포 유지, 뇌신경세포 형성 조절 및 체세포 분화의 시계적 조절에 어떻게 기여하는지 실시간 생물광학 영상 기법을 통해 규명하고 있습니다. 연구는 발달 생물학과 분자 생물학의 융합을 바탕으로, 생체 내 시계적 유전자 네트워크의 동적 메커니즘을 해명하는 데 초점을 맞추고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Embryogenesis involves orchestrated processes of cell proliferation and differentiation. The mammalian Hes basic helix-loop-helix repressor genes play central roles in these processes by maintaining progenitor cells in an undifferentiated state and by regulating binary cell fate decisions. Hes genes also display an oscillatory expression pattern and control the timing of biological events, such as somite segmentation. Many aspects of Hes expression are regulated by Notch signaling, which mediate
The basic helix-loop-helix (bHLH) gene Hes7, a putative Notch effector, encodes a transcriptional repressor. Here, we found that Hes7 expression oscillates in 2-h cycles in the presomitic mesoderm (PSM). In Hes7-null mice, somites are not properly segmented and their anterior-posterior polarity is disrupted. As a result, the somite derivatives such as vertebrae and ribs are severely disorganized. Although expression of Notch and its ligands is not affected significantly, the oscillator and Notch
Notch signaling components such as the basic helix-loop-helix gene Hes1 are cyclically expressed by negative feedback in the presomitic mesoderm (PSM) and constitute the somite segmentation clock. Because Hes1 oscillation occurs in many cell types, this clock may regulate the timing in many biological systems. Although the Hes1 oscillator is stable in the PSM, it damps rapidly in other cells, suggesting that the oscillators in the former and the latter could be intrinsically different. Here, we
Hes genes are mammalian homologues of Drosophila hairy and Enhancer of split, which encode basic helix-loop-helix (bHLH) transcriptional repressors. In the developing central nervous system, Hes1, Hes3 and Hes5 are highly expressed by neural stem cells. Inactivation of these Hes genes leads to upregulation of proneural genes, acceleration of neurogenesis and premature depletion of neural stem cells. Conversely, overexpression of Hes genes leads to inhibition of neurogenesis and maintenance of ne
