The cell cycle dynamics of enteric neural progenitor cells in the context of the extracellular matrix

• Grant number: 22/08697-0
• Support Opportunities: Scholarships abroad - Research
• Start date: May 03, 2023
• End date: May 02, 2024
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Alexandre Bruni Cardoso
• Grantee: Alexandre Bruni Cardoso
• Host Investigator: Rosa Anna Uribe
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Rice University, United States

Abstract

The cell cycle is traditionally studied by means of forcing synchronization in specific cell-cycle phases as well as bulk biochemistry of cells grown on bidimensional surfaces. However, cell proliferation occurs in tridimensional microenvironments within organisms and is rarely synchronized. Recently developed cell-cycle sensors and high-speed 4D microscopy have been overcoming these barriers, allowing long-term videomicroscopy of asynchronous cells at the single-cell level in physiological contexts. The translucid zebrafish larval gut, especially the developing enteric nervous system (ENS), is an excellent model system for studying the cell cycle dynamics of cells in their native microenvironment. The ENS is the largest and most complex portion of the peripheral nervous system and is essential for gut function. Abnormalities of the ENS development, like the Hirschsprung's Disease (HSCR), result in severe chronic constipation, and many HSCR studies have reported abnormal expression of ECM components. Although recent research has identified key transcription factors and signaling pathways regulating ENS development, we still lack a description of the proliferative state of enteric neural progenitor (ENP) while migrating attached to the extracellular matrix. The specific aims of this proposal are to 1. analyze the cell-cycle dynamics at the single-cell level of ENP cells as they migrate into and along the gut of the developing zebrafish and 2. investigate if the cell cycle dynamics of the migrating ENP cells is coupled with changes in the deposition and organization of collagen and laminin. The conclusion of these aims will expand our basic understanding of ENS development, laying the groundwork for translational studies. (AU)