Slug, mammalian homologue gene of Drosophila escargot, promotes neuronal-differentiation through suppression of HEB/daughterless.
At the neuron developmental stage, neuron-precursor cells can be differentiated into neuron or glia cells. However, precise molecular mechanism to determine the cell fate has not been clearly demonstrated. In this study, we reveal that Drosophila esgarcot and its mammalian homologue genes, Snail and Slug, play a key role in neuronal differentiation. In Drosophila model system, overexpression of Esg, like as Wingless, suppresses the bristle formation. In contrast, elimination of Esg though RNAi promotes double bristle phenotype. We can also observe the similar phenotype in Snail-overexpression system. In mammalian system, overexpression of Slug or Snail can induce neuronal differentiation. Esg and its mammalian homologue gene Slug directly interact with Daughtherless and its mammalian homologue HEB and eliminate them through siah-1 mediated protein degradation. Thus, overexpression of siah-1 can promote neuron cell differentiation, whereas si-siah-1 blocks the Slug-induced HEB suppression. In fact, Drosophila SINA, Siah-1 homologue, has been also known to be involved in bristle formation and Neuronal differentiation. In addition, it has been revealed that CK1 is involved in Esg or Snail stability and Neuronal differentiation. However, Snail is regulated only by CK1 but not by Siah. Considering the fact that Slug mutations have been found in human genetic disease, waardenberg syndrome, major symptoms of which is loss of hearing neuron and odd eye, our result implies that slug/Snail system is required for proper neuronal differentiation, like as Esg in Drosophila.
Yang
Dong-Jin
DJ
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, Korea.
Chung
Ji-Yun
JY
Lee
Su-Jin
SJ
Park
So-Young
SY
Pyo
Jung-Hoon
JH
Ha
Nam-Chul
NC
Yoo
Mi-Ae
MA
Park
Bum-Joon
BJ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D047389:Casein Kinase I / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000166:cytology*; D009687:Nuclear Proteins / Q000378:metabolism; D034622:RNA Interference; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000098563:Seven in Absentia Proteins
D051792:Basic Helix-Loop-Helix Proteins; D047389:Casein Kinase I; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; C090080:Da protein, Drosophila; C000604407:SNAI1 protein, human; C467520:esg protein, Drosophila; C000604451:sna protein, Drosophila