New Insights into the Control of Cell Fate Choices and Diﬀerentiation by Retinoic Acid in Cranial, Axial and Caudal Structures

Biomolecules, 2019 · DOI: 10.3390/biom9120860 · Published: December 11, 2019

Simple Explanation

Retinoic acid (RA) is a crucial molecule in chordate development, controlling gene activity and cell differentiation. Its precise regulation, including local degradation, is essential for proper development. RA influences the formation of bones, vertebrae, teeth, and fin regeneration. RA acts as a morphogen, creating signaling gradients that guide cell fate decisions in various developmental processes. Disruptions in RA signaling can lead to defects in facial regions, eyes, heart, and limbs. RA interacts with other signaling pathways like Wnt and Fgf to control the formation of structures like vertebrae and teeth. Understanding how RA regulates these processes is vital for understanding developmental biology and related human diseases.

Study Duration

Not specified

Participants

Zebrafish, mouse and Xenopus embryos

Evidence Level

Review

Key Findings

1
RA signaling gradients control neuromesodermal progenitor (NMP) differentiation into neural or mesodermal tissues. The amount of RA present determines NMP fate.
2
Precisely regulated RA signaling is essential for vertebrae formation in both mammals and fish. RA is also needed for proper calvaria formation (skull bones) and tooth development.
3
RA plays essential roles in zebraﬁsh fin regeneration, influencing blastema formation, osteoblast behavior, and cell fate choices in the preosteoblast lineage. RA controls cell fate in the preosteoblast lineage

Research Summary

This review focuses on recent progress in understanding the roles of retinoic acid (RA) signaling in various developmental processes, with a particular emphasis on zebrafish models. RA signaling gradients are critical for cell fate decisions in neuromesodermal progenitors, vertebrae formation, and fin regeneration. Cyp26 enzymes play a crucial role in creating local RA sinks. Zebrafish models reveal evolutionary modifications in RA-mediated gene regulation, highlighting developmental processes that may be overlooked in mammalian models. Ongoing research aims to further clarify the role of RA in vertebrate development.

Practical Implications

Developmental Biology

Provides insights into the fundamental mechanisms of vertebrate development and cell fate determination.

Human Disease

Offers a better understanding of craniofacial malformations and skeletal anomalies associated with RA signaling disorders.

Regenerative Medicine

Informs strategies for bone regeneration and repair by elucidating the role of RA in osteoblast behavior and fin regeneration.

Study Limitations

1
Studies in zebraﬁsh do not always directly translate to tetrapods.
2
The exact sources of RA in some developmental processes remain unresolved.
3
Further research is needed to fully elucidate the epistatic relationships between RA and FGF signaling.

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