文章基本信息

标题：The Shh/ Gli3 gene regulatory network precedes the origin of paired fins and reveals the deep homology between distal fins and digits
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作者：Joaquín Letelier ; Silvia Naranjo ; Ismael Sospedra-Arrufat 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：46
DOI：10.1073/pnas.2100575118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance In this study, we show that the inactivation of the gli3 gene in medaka fish results in the formation of larger dorsal and paired fins. These mutant fins display multiple radial bones and fin rays which resemble polydactyly in Gli3-deficient mice. Our molecular and genetic analyses indicate that the size of fish fins is controlled by an ancient mechanism mediated by SHH-GLI signaling that appeared prior to the evolutionary appearance of paired fins. We also show that the key regulatory networks that mediate the expansion of digit progenitor cells in tetrapods were already in place in the fins of the last common ancestor between ray and lobe-finned fishes, suggesting an ancient similarity between distal fins and digits. One of the central problems of vertebrate evolution is understanding the relationship among the distal portions of fins and limbs. Lacking comparable morphological markers of these regions in fish and tetrapods, these relationships have remained uncertain for the past century and a half. Here we show that Gli3 functions in controlling the proliferative expansion of distal progenitors are shared among dorsal and paired fins as well as tetrapod limbs. Mutant knockout gli3 fins in medaka ( Oryzias latipes) form multiple radials and rays, in a pattern reminiscent of the polydactyly observed in Gli3-null mutant mice. In limbs, Gli3 controls both anterior–posterior patterning and cell proliferation, two processes that can be genetically uncoupled. In situ hybridization, quantification of proliferation markers, and analysis of regulatory regions reveal that in paired and dorsal fins, gli3 plays a main role in controlling proliferation but not in patterning. Moreover, gli3 down-regulation in shh mutant fins rescues fin loss in a manner similar to how Gli3 deficiency restores digits in the limbs of Shh mutant mouse embryos. We hypothesize that the Gli3/Shh gene pathway preceded the origin of paired appendages and was originally involved in modulating cell proliferation. Accordingly, the distal regions of dorsal fins, paired fins, and limbs retain a deep regulatory and functional homology that predates the origin of paired appendages.
关键词：fin growth; Gli3; Shh; fin-to-limb transition