Prof. Nissim Ben-Arie
Nissim Ben-Arie has a B.Sc. in Biology and M.Sc. in Biological Chemistry (both from the Hebrew University of Jerusalem, Israel), and a Ph.D. in Molecular and Human Genetics (from the Weizmann Institute of Science, Israel). He started studying brain development as a postdoctoral fellow in the lab of Huda Zoghbi (Baylor College of Medicine, Houston, TX, USA), where he established the essential role of Math1 in neurogenesis, particularly in the cerebellum. He is currently a researcher at the Institute of Life Sciences at the Hebrew University of Jerusalem. He has served as the Head of the Teaching Program and later as the Chairman of the Department of Cell and Developmental Biology. He is currently studying the molecular and cellular mechanisms regulating the development of spinal cord and midbrain dopaminergic systems.
An organism contains a vast number of cells, which are divided into numerous cell types, each at the correct number, precise position and desired interactions with other cells. We focus on revealing the genetic regulation of fate acquisition and understanding of the multi-step process of differentiation towards the fate of choice.
During embryonic development, when a relatively-naiive mother cell divides, one of the daughter cells may become a next-generation mother cell, while its sister may undertake a differentiation path. At this point bHLH (basic Helix-Loop-Helix) transcription factors start acting, and play an essential role in guiding the multi-step process of differentiation.
Two complementing aspects are at the center of our interest: normal embryonic development and pathologies & diseases that emerge when the bHLH genes are mutated or deleted. Our research is multidisciplinary and involves mouse and human genetics, neuroscience, molecular and cellular biology, and embryology. Our model systems are the chick embryo and genetically-engineered mice.
We study three bHLH transcription factors: Math1, Nato3, and Fingerin. Each factor is expressed in a distinct tissue and regulates the emergence of discrete groups of cells. Math1 is crucial for the development of granule neurons of the cerebellum and specific interneurons in the spinal cord. Abnormal expression may lead in childhood to medulloblastoma, a common tumor of the cerebellum. Nato3 regulates the differentiation of floor plate cells, a unique population of cells in the emerging spinal cord and mid-brain. When Nato3 is deleted from the mouse genome, mouse pups are born with a reduced population of dopaminergic neurons. Interestingly, these are the same neurons that degenerate in Parkinson’s disease and function abnormally in additional movement disorders.
Mansour AA, Nissim-Eliraz E, Zisman S, Golan-Lev T, Schatz O, Klar A and Ben-Arie N (2011). Foxa2 regulates the expression of Nato3 in the floor plate by a novel evolutionarily-conserved promoter. Mol. Cell. Neuroscience 46: 187-19
Nissim-Eliraz E and Ben-Arie N (2013). Nato3 integrates with the Shh-Foxa2 transcriptional network regulating the differentiation of midbrain dopaminergic neurons. J Mol. Neurosci. 51:13-27.
Mansour AA, Khazanov-Zisman S, Klar A and Ben-Arie N. (2014) Nato3 plays an integral role in dorsoventral patterning of the spinal cord by segregating floor plate/p3 fates via Nkx2.2 suppression and Foxa2 maintenance. Development 141: 574-584.
Schatz O, Langer E, and Ben-Arie N. (2014) .Gene dosage of the transcription factor Fingerin (bHLHA9) affects digit development and links syndactyly to ectrodactyly. Human Mol. Genetics 23: 5394-5401