Retinoic acid, a key morphogen in early vertebrate development and tissue regeneration, mediates its effects through the binding of receptors that act as ligand-induced transcription factors. These binding events function to recruit an array of transcription co-regulatory proteins to specific gene promoters. One such co-regulatory protein, neuronal proliferation and differentiation control-1 (NPDC-1), is broadly expressed during mammalian development and functions as an in vitro repressor of retinoic acid receptor (RAR)-mediated transcription. To obtain comparative and developmental insights about NPDC-1 function, we cloned the axolotl (Ambystoma mexicanum) orthologue and measured transcript abundances among tissues sampled during the embryonic and juvenile phases of development, and also during spinal cord regeneration. Structurally, the axolotl orthologue of NPDC-1 retained sequence identity to mammalian sequences in all functional domains. Functionally, we observed that axolotl NPDC-1 mRNA expression peaked late in embryogenesis, with highest levels of expression occurring during the time of limb development, a process regulated by retinoic acid signaling. Also similar to what has been observed in mammals, axolotl NPDC-1 directly interacts with axolotl RAR, modulates axolotl RAR DNA binding, and represses cell proliferation and axolotl RAR-mediated gene transcription. These data justify axolotl as a model to further investigate NPDC-1 and its role in regulating retinoic acid signaling.
|Number of pages||11|
|Journal||Comparative Biochemistry and Physiology - B Biochemistry and Molecular Biology|
|State||Published - Jun 2007|
Bibliographical noteFunding Information:
These studies were supported by grants from the National Institutes of Health (NIH) (HL67321), the LAM Foundation (LAM052), and the Kentucky Lung Cancer Research Program to D.J.N. Aspects of this project were also supported by grants to S.R.V.: IBN-0242833 from the National Science Foundation (NSF) CAREER Award program and grant number 5-R24-RR016344-06 from the National Center for Research Resources (NCRR), a component of the NIH. We also acknowledge the support of the NSF funded Ambystoma Genetic Stock Center at University of Kentucky.
- Ambystoma mexicanum
- Retinoic acid
- Retinoic acid receptor
- Transcription factor
ASJC Scopus subject areas
- Molecular Biology