Retinoic Acid Receptors and the Control of Positional Information in the Regenerating Axolotl Limb.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Ambystoma mexicanum/*metabolism ; Extremities/*physiology ; Receptors, Retinoic Acid/*metabolism ; Regeneration/*physiology; Animals ; Extracellular Matrix/metabolism ; Mesoderm/metabolism ; Mesoderm/physiology ; Signal Transduction/physiology ; Tretinoin/metabolism

We know little about the control of positional information (PI) during axolotl limb regeneration, which ensures that the limb regenerates exactly what was amputated, and the work reported here investigates this phenomenon. Retinoic acid administration changes the PI in a proximal direction so that a complete limb can be regenerated from a hand. Rather than identifying all the genes altered by RA treatment of the limb, we have eliminated many off-target effects by using retinoic acid receptor selective agonists. We firstly identify the receptor involved in this respecification process as RARα and secondly, identify the genes involved by RNA sequencing of the RARα-treated blastemal mesenchyme. We find 1177 upregulated genes and 1403 downregulated genes, which could be identified using the axolotl genome. These include several genes known to be involved in retinoic acid metabolism and in patterning. Since positional information is thought to be a property of the cell surface of blastemal cells when we examine our dataset with an emphasis on this aspect, we find the top canonical pathway is integrin signaling. In the extracellular matrix compartment, we find a MMP and several collagens are upregulated; several cell membrane genes and secretory factors are also upregulated. This provides data for future testing of the function of these candidates in the control of PI during limb regeneration.

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1558017 National Science Foundation

Keywords: RARα; axolotl; limb regeneration; positional information; retinoic acid; retinoic acid receptor

0 (Receptors, Retinoic Acid)
5688UTC01R (Tretinoin)

Date Created: 20210928 Date Completed: 20211119 Latest Revision: 20211119

20231215

PMC8469983

10.3390/cells10092174

34571821