Operating principles of Notch-Delta-Jagged module of cell-cell communication

Autor(es)

Jolly, Mohit Kumar ^{[1, 2]} ; Boareto, Marcelo ^{[3, 1]} ; Lu, Mingyang ^[1] ; Onuchic, Jose'N ^{[4, 1, 5, 6]} ; Clementi, Cecilia ^{[4, 1]} ; Ben-Jacob, Eshel ^{[1, 5, 7, 8]}

Afiliação do(s) autor(es)

^[1] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA

^[2] Rice Univ, Dept Bioengn, Houston, TX 77005 - USA

^[3] Univ Sao Paulo, Inst Phys, BR-05508 Sao Paulo - Brazil

^[4] Rice Univ, Dept Chem, Houston, TX 77005 - USA

^[5] Rice Univ, Dept Biosci, Houston, TX 77005 - USA

^[6] Rice Univ, Dept Phys & Astron, Houston, TX 77005 - USA

^[7] Tel Aviv Univ, Sch Phys & Astron, IL-69978 Tel Aviv - Israel

^[8] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv - Israel

• Tipo de documento: Artigo Científico
• Fonte: NEW JOURNAL OF PHYSICS; v. 17, MAY 20 2015.
• Citações Web of Science: 12

Resumo

Notch pathway is an evolutionarily conserved cell-cell communication mechanism governing cell-fate during development and tumor progression. It is activated when Notch receptor of one cell binds to either of its ligand-Delta or Jagged-of another cell. Notch-Delta (ND) signaling forms a two-way switch, and two cells interacting via ND signaling adopt different fates-Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Notch-Delta-Jagged signaling (NDJ) behaves as a three-way switch and enables an additional fate-hybrid Sender/Receiver (S/R) (medium ligand, medium receptor). Here, by extending our framework of NDJ signaling for a two-cell system, we show that higher production rate of Jagged, but not that of Delta, expands the range of parameters for which both cells attain the hybrid S/R state. Conversely, glycosyltransferase Fringe and cis-inhibition reduces this range of conditions, and reduces the relative stability of the hybrid S/R state, thereby promoting cell-fate divergence and consequently lateral inhibition-based patterns. Lastly, soluble Jagged drives the cells to attain the hybrid S/R state, and soluble Delta drives them to be Receivers. We also discuss the critical role of hybrid S/R state in promoting cancer metastasis by enabling collective cell migration and expanding cancer stem cell (CSC) population. (AU)

• Processo FAPESP: 13/14438-8 - Estudo de redes gênicas regulatórias por meio de métodos estocásticos e de mecânica estatística
• Beneficiário: Marcelo Boareto Do Amaral
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto