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Determination

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...

General Transcription Factors

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

TGF - β Signaling Pathway

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...

Bone Remodeling and Repair

Bone Remodeling and Repair

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...

Bone Formation by Endochondral Ossification

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...

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Related Experiment Video

Updated: Jul 21, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

Published on: March 15, 2016

Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2.

E Zelzer¹, D J Glotzer, C Hartmann

¹Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

Mechanisms of Development

|July 27, 2001

Summary

Cbfa1/Runx2 is essential for vascular endothelial growth factor (VEGF) expression during bone development. Targeting Cbfa1 prevents VEGF upregulation and blood vessel formation in cartilage, highlighting its role in angiogenesis.

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Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis

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Last Updated: Jul 21, 2026

A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors

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Published on: March 15, 2016

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

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Published on: May 31, 2016

Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis

Laser Capture Microdissection of Mouse Embryonic Cartilage and Bone for Gene Expression Analysis

Published on: December 18, 2019

Area of Science:

Molecular Biology
Developmental Biology
Genetics

Background:

Vascular endothelial growth factor (VEGF) is crucial for angiogenesis, but its expression regulation is not fully understood.
Endochondral bone formation involves blood vessel invasion into cartilage, linked to VEGF and its receptors.

Purpose of the Study:

To investigate the role of Cbfa1/Runx2 in regulating VEGF expression during endochondral bone formation.
To determine if Cbfa1/Runx2 is a key factor controlling tissue-specific VEGF expression.

Main Methods:

Analysis of VEGF expression in Cbfa1-deficient mice.
Over-expression of Cbfa1 in fibroblasts to assess its effect on VEGF production.

Main Results:

Cbfa1 deficiency resulted in a specific loss of VEGF expression in hypertrophic chondrocytes.
Cartilage angiogenesis was absent in Cbfa1-deficient mice due to lack of VEGF upregulation.
Over-expression of Cbfa1 increased VEGF mRNA and protein levels in fibroblasts by stimulating transcription.

Conclusions:

Cbfa1/Runx2 is a necessary regulator of VEGF expression in the context of endochondral bone formation.
Cbfa1 plays a critical role in the tissue-specific genetic program controlling VEGF during skeletal development.