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.
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.
- Fingerin is important for the development of the most distal parts of the hands and feet. Mice lacking Fingerin are born with syndactyly, and display fused fingers. A mirror phenotype is seen in humans that have an extra copy of the gene and are consequently born with lobster-like hands.