Related Experiment Videos
The developmental expression in the rat CNS and peripheral tissues of proteases PC5 and PACE4 mRNAs: comparison with
M Zheng1, N G Seidah, J E Pintar
1Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Insights
Two prohormone convertase (PC) enzymes, PC5 and PACE4, show unique prenatal expression patterns. Their distinct spatial and temporal localization suggests they process different substrates during development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Peptides regulating cellular growth and differentiation are synthesized as precursors.
- Proteolytic processing by prohormone convertases (PCs) is essential for precursor maturation.
- Two PC family members, PC5 and PACE4, were recently identified.
Purpose of the Study:
- To determine the prenatal expression patterns of PC5 and PACE4.
- To compare the expression of PC5 and PACE4 with previously characterized PCs.
- To investigate the potential roles of PC5 and PACE4 in developmental processes.
Main Methods:
- In situ hybridization was used to detect PC5 and PACE4 mRNA expression.
- Expression patterns were analyzed across various embryonic and midgestational stages.
- Localization was examined in both the developing nervous system and peripheral tissues.
Main Results:
- PC5 and PACE4 exhibit unique and distinct prenatal spatial and temporal expression patterns.
- PC5 mRNA is detected early in the neural tube, myotomes, and uterus, expanding to the nervous system by midgestation.
- PACE4 mRNA shows distinct expression in the developing nervous system, particularly the hippocampus, and in peripheral organs like the heart and liver.
- Complementary expression patterns of PC5 and PACE4 were observed in peripheral organ systems such as the lung and gut.
Conclusions:
- PC5 and PACE4 play significant roles in neuropeptide precursor processing during development.
- The nonoverlapping expression patterns suggest PC5 and PACE4 may target distinct sets of proprotein substrates.
- These findings provide insights into the specific functions of PC5 and PACE4 in the developing nervous system and peripheral tissues.
Abstract:
Many peptides modulating cellular growth and differentiation in development are first synthesized as precursors that require proteolytic processing by the "prohormone convertase" (PC) family of endoproteases. Using in situ hybridization, we have here determined that two recently identified PC members, PC5 and PACE4, are expressed prenatally in spatial and temporal patterns that are each unique and distinct from those of previously characterized PCs. PC5 mRNA is first detected at e9 in highly restricted regions of the neural tube, in caudal myotomes, and at the materno-embryonic junction of the uterus. At e10, restricted PC5 mRNA expression is detected in the optic and otic vesicles, the roof of midbrain, and trunk myotomes. By midgestation (e13-e16), PC5 mRNA expression in the developing nervous system has expanded to multiple regions including hippocampus, thalamus, hypothalamus, brain stem, and spinal cord. By midgestational stages, PACE4 mRNA is expressed in multiple regions of the developing nervous system, generally distinct from PC5, and including a uniquely high level of expression in the ventricular zone of the hippocampus. In several peripheral organ systems, including lung and gut, we observed remarkably complementary patterns of PC5 and PACE4 expression. In addition, PACE4 transcripts are expressed in the heart and liver, whereas PC5 is expressed in the adrenal and kidney primordia. These results suggest that both PC5 and PACE4 may be involved in neuropeptide precursor processing in the developing nervous system and peripheral tissues with the general nonoverlapping expression patterns suggesting that PC5 and PACE4 may process distinct sets of proprotein substrates.