Zheng M, Seidah N G, Pintar J E
Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Dev Biol. 1997 Jan 15;181(2):268-83. doi: 10.1006/dbio.1996.8402.
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.
许多在发育过程中调节细胞生长和分化的肽最初是以前体形式合成的，这些前体需要由“激素原转化酶”（PC）家族的内切蛋白酶进行蛋白水解加工。通过原位杂交，我们在此确定了最近鉴定出的两种PC成员，即PC5和PACE4，在产前以独特的时空模式表达，这些模式与先前已表征的PCs不同。PC5 mRNA最早在胚胎第9天在神经管的高度受限区域、尾侧肌节以及子宫的母胎交界处被检测到。在胚胎第10天，在视泡和听泡、中脑顶部以及躯干肌节中检测到受限的PC5 mRNA表达。到妊娠中期（胚胎第13 - 16天），PC5 mRNA在发育中的神经系统中的表达已扩展到多个区域，包括海马体、丘脑、下丘脑、脑干和脊髓。在妊娠中期阶段，PACE4 mRNA在发育中的神经系统的多个区域表达，通常与PC5不同，并且在海马体的室管膜区有独特的高表达水平。在包括肺和肠道在内的几个外周器官系统中，我们观察到PC5和PACE4表达的显著互补模式。此外，PACE4转录本在心脏和肝脏中表达，而PC5在肾上腺和肾脏原基中表达。这些结果表明，PC5和PACE4可能都参与了发育中的神经系统和外周组织中神经肽前体的加工，其总体不重叠的表达模式表明PC5和PACE4可能加工不同的前蛋白底物组。
