GO:0035907 dorsal aorta development: Vascular Development, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035907 dorsal aorta development describes the progression of the dorsal aorta from its initial formation to the mature structure in a single-pass circulatory system.
• The dorsal aorta forms through separate origins, lateral-to-medial migration of angioblasts, and subsequent remodeling into a mature vessel.
• VEGF signaling mediates angioblast migration during dorsal aorta development, as demonstrated in Xenopus embryos.
• Blood flow mechanosensing via Plxnd1 and Klf2 controls the caliber of the dorsal aorta, linking hemodynamics to vessel morphogenesis.
• The dorsal aorta is a key site for hematopoietic stem cell emergence, with polarization of the vessel being critical for this process.
• Disruptions in dorsal aorta development are linked to congenital aortic arch anomalies and vascular malformations.
Description
The dorsal aorta is the primary artery in the single-pass circulatory system of organisms such as fish and amphibians, carrying oxygenated blood from the gills to the rest of the body. Its development, formally annotated as GO:0035907 dorsal aorta development, encompasses the progression of this vessel from its initial formation to a mature structure. Understanding this process is fundamental for developmental biologists, vascular researchers, and clinicians studying congenital vascular defects. The dorsal aorta serves not only as a conduit for blood but also as a critical niche for hematopoietic stem cell emergence, making its development a focal point for studies in hematopoiesis and vascular biology. Research over the past decades has elucidated that the dorsal aorta forms from multiple angioblast populations that migrate and coalesce, a process tightly regulated by signaling pathways such as VEGF. Moreover, once formed, the vessel undergoes remodeling and acquires its final caliber through mechanosensitive mechanisms that sense blood flow. These findings underscore the complexity of dorsal aorta development and its importance in both normal physiology and disease.
dorsal aorta development At A Glance
| GO ID | GO:0035907 |
|---|---|
| GO term | dorsal aorta development |
| Ontology | biological_process |
| Synonym | none |
| Major function | Formation and maturation of the dorsal aorta, the main artery in single-pass circulatory systems |
| Key signaling pathways | VEGF signaling mediates angioblast migration; Plxnd1-Klf2 mechanosensing controls vessel caliber |
| Developmental origin | Separate origins with lateral-to-medial migration of angioblasts |
| Associated processes | Hematopoietic stem cell emergence from hemogenic endothelium |
What Is GO:0035907?
GO:0035907 dorsal aorta development is defined as the progression of the dorsal aorta over time, from its initial formation to the mature structure. The dorsal aorta is a blood vessel in a single-pass circulatory system that carries oxygenated blood from the gills to the rest of the body. In a single-pass circulatory system, blood passes once through the heart to supply the body once.
Why Is dorsal aorta development Important in Cell Biology?
Dorsal aorta development is critically important because the dorsal aorta is not only the principal conduit for oxygenated blood in organisms with single-pass circulation but also a transient hematopoietic organ where hematopoietic stem cells emerge. Defects in its formation or remodeling can lead to congenital cardiovascular anomalies, including aortic arch malformations. Furthermore, understanding the molecular and cellular mechanisms of dorsal aorta development provides insights into general principles of angiogenesis, vessel patterning, and mechanotransduction, which are relevant to human vascular diseases and regenerative medicine.
• The dorsal aorta is the main artery in single-pass circulatory systems, essential for systemic oxygen delivery.
• It serves as the site of hematopoietic stem cell emergence, linking vascular development to blood formation.
• VEGF-mediated angioblast migration is a paradigm for understanding growth factor-guided cell movement.
• Mechanosensing by Plxnd1 and Klf2 in the dorsal aorta reveals how blood flow shapes vessel caliber.
• Congenital aortic arch anomalies arise from disrupted dorsal aorta and pharyngeal arch artery development.
• Dorsal aorta development is a model for studying lateral-to-medial migration and vessel remodeling.
• Insights from dorsal aorta development inform tissue engineering of vascular grafts.
• The process is conserved across vertebrates, allowing use of model organisms to study human vascular biology.
• Hematopoietic stem cell emergence from the dorsal aorta is critical for lifelong blood production.
• Dysregulation of dorsal aorta development is implicated in vascular malformations and aneurysms.
What Happens During dorsal aorta development?
Angioblast specification and migration
In simple terms: Cells that will become blood vessel lining are told where to go and move to the right place.
During early embryogenesis, angioblasts (endothelial precursor cells) are specified from mesoderm and migrate to form the dorsal aorta. In Xenopus, VEGF signaling mediates the migration of angioblasts toward the midline, a critical step for dorsal aorta formation. These angioblasts originate from separate regions and undergo lateral-to-medial migration to coalesce into a primitive vessel.
Vessel assembly and lumen formation
In simple terms: The migrating cells stick together and form a hollow tube.
Once angioblasts reach the midline, they assemble into a cord and subsequently form a lumen, creating a functional blood vessel. This process involves cell-cell adhesion, polarization, and the establishment of apicobasal polarity. The dorsal aorta polarizes, a feature that is essential for its later function in hematopoietic stem cell emergence. The initial formation of the dorsal aorta from separate origins and its remodeling into a mature structure are key aspects of GO:0035907.
Remodeling and caliber control
In simple terms: The vessel adjusts its size based on blood flow.
After initial formation, the dorsal aorta undergoes remodeling to acquire its final caliber. Blood flow is sensed by endothelial cells through mechanosensory mechanisms involving Plxnd1, which regulates the transcription factor Klf2 to control vessel caliber. This flow-dependent remodeling ensures the dorsal aorta matches the circulatory demands of the growing embryo.
Hematopoietic stem cell emergence
In simple terms: The dorsal aorta gives birth to blood stem cells.
The dorsal aorta is a hemogenic endothelium, meaning it produces hematopoietic stem cells. The polarization of the dorsal aorta is critical for hematopoietic stem cell emergence, as highlighted by studies showing that the transition of signal requirements in hematopoietic stem cell development from hemogenic endothelial cells occurs in this region. This process links dorsal aorta development directly to the establishment of the adult blood system.
Key Genes Involved in GO:0035907 dorsal aorta development
The following genes and proteins are key players in dorsal aorta development, as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| VEGF | Mediates angioblast migration during dorsal aorta development | Studying angioblast guidance and vascular patterning |
| Plxnd1 | Mechanosensing of blood flow to control dorsal aorta caliber | Understanding flow-dependent vessel remodeling |
| Klf2 | Transcription factor downstream of Plxnd1 in caliber control | Investigating mechanotransduction in endothelium |
| Notch | Involved in hematopoietic stem cell emergence from hemogenic endothelium | Studying hemogenic endothelium and HSC specification |
| Runx1 | Essential for hematopoietic stem cell emergence from dorsal aorta | Modeling HSC development and leukemia |
| Scl/Tal1 | Required for hemogenic endothelium and HSC emergence | Understanding blood development |
| Gata2 | Regulates hemogenic endothelium gene programs | Investigating HSC emergence |
| Cdh5 | Endothelial adherens junction protein, important for vessel integrity | Studying endothelial cell-cell adhesion |
| Tie2 | Angiopoietin receptor, regulates vessel remodeling | Investigating angiogenesis and vessel stabilization |
| EphrinB2 | Arterial marker and regulator of vessel patterning | Studying arterial-venous specification |
| Dll4 | Notch ligand involved in arterial specification | Understanding arterial fate |
| Sox17 | Endothelial transcription factor | Investigating endothelial differentiation |
| Etv2 | Master regulator of endothelial development | Studying angioblast specification |
| Foxc1/2 | Required for aortic arch and dorsal aorta development | Modeling congenital aortic arch defects |
| Pax3 | Neural crest regulator affecting aortic arch remodeling | Studying neural crest contribution to vessels |
| Tbx1 | Implicated in aortic arch anomalies | Investigating DiGeorge syndrome |
| Retinoic acid signaling | Patterning of dorsal aorta along anterior-posterior axis | Understanding vascular patterning |
How Is dorsal aorta development Regulated?
Dorsal aorta development is regulated by multiple signaling pathways and mechanical forces. VEGF signaling is a key regulator of angioblast migration, as shown in Xenopus where VEGF mediates the movement of angioblasts to form the dorsal aorta. Blood flow itself acts as a regulatory input: mechanosensing via Plxnd1 controls the transcription factor Klf2, which in turn regulates the caliber of the dorsal aorta. Additionally, the transition of signal requirements in hematopoietic stem cell development from hemogenic endothelial cells in the dorsal aorta suggests that Notch and other signaling pathways are dynamically regulated during this process. The polarization of the dorsal aorta is also a regulated event critical for hematopoietic stem cell emergence.
dorsal aorta development and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Tbx1 | DiGeorge syndrome / aortic arch anomalies | Knockout mouse or zebrafish to study aortic arch patterning |
| Plxnd1 | Vascular malformations / aneurysm | Point mutation knock-in in zebrafish to alter mechanosensing |
| Runx1 | Hematopoietic stem cell failure / leukemia | Conditional knockout in mouse dorsal aorta |
| VEGF | Angiogenesis defects / vascular insufficiency | Overexpression or knockout in Xenopus or zebrafish |
| Foxc1/2 | Congenital aortic arch defects | Knockout mouse to model arch artery anomalies |
Congenital aortic arch anomalies
Disruptions in the development of the dorsal aorta and its derivatives, the aortic arches, lead to congenital cardiovascular defects such as interrupted aortic arch, double aortic arch, and vascular rings. These anomalies often arise from defects in neural crest cells and their interactions with the pharyngeal arch arteries, which are remodeled from the dorsal aorta. Cardiac neural crest cells play a crucial role in patterning the aortic arch arteries, and their dysfunction is linked to human syndromes such as DiGeorge syndrome.
Hematopoietic stem cell disorders
The dorsal aorta is the site of hematopoietic stem cell emergence, and defects in this process can lead to severe blood disorders. The polarization of the dorsal aorta and the transition of signal requirements in hematopoietic stem cell development from hemogenic endothelial cells are critical steps; their failure may result in hematopoietic stem cell deficiencies or leukemias. Understanding these mechanisms has implications for regenerative medicine and bone marrow transplantation.
Vascular malformations and aneurysms
Abnormal mechanosensing in the dorsal aorta, involving Plxnd1 and Klf2, can lead to improper caliber control and potentially contribute to vascular malformations or aneurysms. The dorsal aorta serves as a model to study how blood flow regulates vessel diameter, and its dysregulation may underlie human vascular pathologies such as aortic aneurysms.
From dorsal aorta development-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate angioblast migration? | Knockout of gene X in Xenopus or zebrafish, followed by live imaging |
| Does a point mutation in Plxnd1 alter mechanosensing? | Point mutation knock-in in zebrafish, measure dorsal aorta caliber |
| Is gene Y required for hematopoietic stem cell emergence? | Conditional knockout in mouse hemogenic endothelium |
| Does overexpression of VEGF increase dorsal aorta size? | Overexpression of VEGF in Xenopus embryos |
| Does a tagged Klf2 knock-in reveal its localization? | Tagged knock-in of Klf2 in zebrafish, imaging |
| Does gene Z affect aortic arch patterning? | Knockout mouse with neural crest-specific deletion |
How to Study the dorsal aorta development Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live fluorescence imaging | Angioblast migration and vessel formation | Tracking dorsal aorta development in zebrafish |
| Single-cell RNA-seq | Gene expression heterogeneity | Identifying hemogenic endothelium in dorsal aorta |
| Lineage tracing | Cell origins and fate | Determining separate origins of dorsal aorta |
| Microfluidic flow assays | Endothelial response to shear stress | Studying Plxnd1/Klf2 mechanosensing |
| In situ hybridization | Spatial gene expression | Localizing VEGF during dorsal aorta development |
| CRISPR-Cas9 knockout | Gene function | Testing requirement of genes in dorsal aorta development |
| Pharmacological inhibition | Pathway activity | Blocking VEGF signaling to assess migration |
| Electron microscopy | Ultrastructure of vessel | Examining lumen formation and cell junctions |
Live imaging of dorsal aorta development
Live imaging using fluorescently labeled endothelial cells allows visualization of angioblast migration, vessel assembly, and remodeling in real time. This method has been used to track dorsal aorta formation in zebrafish and Xenopus, revealing lateral-to-medial migration and lumen formation.
Transcriptomics and single-cell RNA sequencing
RNA sequencing of endothelial cells isolated from the dorsal aorta at different developmental stages can identify gene expression programs driving specification, migration, and hematopoietic stem cell emergence. Single-cell RNA-seq has been used to dissect the heterogeneity of hemogenic endothelium in the dorsal aorta.
Genetic lineage tracing
Lineage tracing using Cre-lox or similar systems in mice allows researchers to determine the contribution of different cell populations to the dorsal aorta. This approach has been valuable in understanding the separate origins of dorsal aorta endothelial cells.
Mechanotransduction assays
To study flow-dependent regulation of dorsal aorta caliber, researchers use microfluidic devices or in vivo models with altered blood flow. These assays have implicated Plxnd1 and Klf2 in mechanosensing.
How CRISPR Can Be Used to Study GO:0035907 dorsal aorta development
Knockout
CRISPR-Cas9 knockout of candidate genes in model organisms such as zebrafish or mice can determine their requirement for dorsal aorta development. For example, knocking out runx1 or scl in zebrafish has been used to study hematopoietic stem cell emergence from the dorsal aorta. Knockout of plxnd1 or klf2 can reveal their roles in caliber control.
Point Mutation
Introducing specific point mutations via CRISPR base editing or homology-directed repair allows researchers to model human disease variants or dissect protein function. For instance, point mutations in Plxnd1 that affect mechanosensing can be knocked into the zebrafish genome to study their impact on dorsal aorta caliber.
Knock-in
Knock-in of reporter genes or tags (e.g., GFP, mCherry) into endogenous loci enables visualization of gene expression and protein localization. Tagged knock-in of klf2 or plxnd1 in zebrafish allows live imaging of their expression during dorsal aorta development. Knock-in of Cre recombinase into endothelial-specific genes facilitates lineage tracing.
Overexpression
CRISPR activation (CRISPRa) or transgenic overexpression can be used to study the effects of increased gene dosage. Overexpression of VEGF in Xenopus embryos leads to enlarged dorsal aortae, demonstrating its role in angioblast migration. Similarly, overexpression of klf2 can alter vessel caliber.
How EDITGENE Supports dorsal aorta development Research
Researchers studying dorsal aorta development-related genes often need to determine whether a candidate gene is causally involved in vessel formation, remodeling, or hematopoietic stem cell emergence. EDITGENE provides comprehensive CRISPR-based services to create precisely engineered cell and animal models, enabling functional validation of genes implicated in GO:0035907 dorsal aorta development.
Contact EDITGENE today to design your custom CRISPR model for dorsal aorta development research.
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Frequently Asked Questions About dorsal aorta development
What is GO:0035907 dorsal aorta development?
GO:0035907 is a Gene Ontology biological process term that describes the progression of the dorsal aorta from its initial formation to the mature structure. The dorsal aorta is the main artery in a single-pass circulatory system, carrying oxygenated blood from the gills to the body.
What genes are involved in dorsal aorta development?
Key genes include VEGF, which mediates angioblast migration; Plxnd1 and Klf2, which control vessel caliber via mechanosensing; and Runx1, Scl, and Gata2, which are critical for hematopoietic stem cell emergence from the dorsal aorta.
How does the dorsal aorta form?
The dorsal aorta forms through separate origins, with angioblasts migrating laterally to medially and coalescing into a vessel, followed by remodeling and lumen formation. VEGF signaling guides this migration.
What is the role of blood flow in dorsal aorta development?
Blood flow is sensed by endothelial cells through Plxnd1, which regulates Klf2 to control the caliber of the dorsal aorta, ensuring proper vessel size.
Why is the dorsal aorta important for blood development?
The dorsal aorta is a hemogenic endothelium where hematopoietic stem cells emerge, a process critical for establishing the blood system.
What diseases are associated with abnormal dorsal aorta development?
Disruptions can lead to congenital aortic arch anomalies such as interrupted aortic arch and DiGeorge syndrome, as well as vascular malformations and hematopoietic defects.
What model organisms are used to study dorsal aorta development?
Zebrafish, Xenopus, and mouse are commonly used due to their conserved vascular development and genetic tractability.
How can CRISPR be used to study dorsal aorta development?
CRISPR can create knockouts, point mutations, knock-ins, and overexpression models in endothelial cells or model organisms to test gene function in dorsal aorta formation and remodeling.
What is the role of VEGF in dorsal aorta development?
VEGF mediates the migration of angioblasts during dorsal aorta formation, as demonstrated in Xenopus embryos.
What is the significance of dorsal aorta polarization?
Polarization of the dorsal aorta is critical for hematopoietic stem cell emergence, linking vessel architecture to blood stem cell production.
Conclusion
GO:0035907 dorsal aorta development is a fundamental biological process that encompasses the formation, remodeling, and maturation of the dorsal aorta, a vessel critical for circulation and hematopoietic stem cell emergence. Research using model organisms and advanced genetic tools has elucidated key roles for VEGF, Plxnd1, Klf2, and hematopoietic transcription factors in this process. Understanding dorsal aorta development not only sheds light on congenital vascular diseases but also informs regenerative strategies for blood and vascular disorders. Continued investigation using CRISPR-based models and multi-omics approaches will further unravel the complex regulation of this essential developmental event.
References
- 2. Yamagishi H. 2021. Cardiac Neural Crest.. Cold Spring Harb Perspect Biol 13(1) PMID: 32071091
- 3. Rosen RD et al.. 2026. Embryology, Aortic Arch.. PMID: 31985966
- 4. Yvernogeau L et al.. 2023. Dorsal aorta polarization and haematopoietic stem cell emergence.. Development 150(1) PMID: 36602140
- 6. Sato Y. 2013. Dorsal aorta formation: separate origins, lateral-to-medial migration, and remodeling.. Dev Growth Differ 55(1):113-29 PMID: 23294360
- 7. He J et al.. 2024. Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2.. bioRxiv PMID: 38328196
- 8. Cleaver O et al.. 1998. VEGF mediates angioblast migration during development of the dorsal aorta in Xenopus.. Development 125(19):3905-14 PMID: 9729498
