Related Experiment Video
Updated: Jul 14, 2026
09:25
Live Imaging of Mitosis in the Developing Mouse Embryonic Cortex
Published on: June 4, 2014
Cell cycle regulator E2F4 is essential for the development of the ventral telencephalon
Vladimir A Ruzhynsky1, Kelly A McClellan, Jacqueline L Vanderluit
1Department of Cellular and Molecular Medicine, Ottawa Health Research Institute, Neuroscience Program, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5.
Summary
The cell cycle regulator E2F4 is crucial for early brain development. Its deficiency impairs neural stem cell renewal and leads to the loss of ventral telencephalic structures by reducing Sonic hedgehog (Shh) expression.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Early forebrain development involves complex neural precursor proliferation and structural changes.
- Mechanisms integrating these processes remain poorly understood.
Purpose of the Study:
- To investigate the role of the cell cycle regulatory protein E2F4 in early forebrain development.
- To elucidate the molecular mechanisms underlying E2F4's function in ventral telencephalon development.
Main Methods:
- Analysis of E2F4-deficient mice models.
- Investigation of Sonic hedgehog (Shh) expression levels.
- Genetic interaction studies with Shh pathway.
- Functional rescue experiments using a Hh agonist.
- Assessment of Shh enhancer activity.
Main Results:
- E2F4 deficiency causes loss of ventral telencephalic structures and impairs neural precursor self-renewal.
- A significant reduction in Sonic hedgehog (Shh) expression was observed in E2F4-deficient ventral telencephalon.
- Genetic studies revealed an interaction between E2F4 and Shh pathways.
- Hh agonist treatment rescued stem cell self-renewal and ventral patterning markers.
- E2F4 deficiency led to impaired activity of Shh forebrain-specific enhancers.
Conclusions:
- E2F4 is essential for the proper development of the ventral telencephalon.
- E2F4 regulates ventral forebrain patterning through modulation of Shh expression and enhancer activity.
- This study reveals a novel role for E2F4 in integrating cell cycle regulation with developmental signaling pathways.
Related Concept Videos
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:28The Cell Cycle Control System
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
02:38Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
01:27Molecular Factors Affecting Cell Division
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...