The problem of the origin of primordial germ cells (PGCs) in vertebrates: historical review and a possible solution GIOVANNI PILATO*, VERA D’URSO, FABIO VIGLIANISI, FRANCESCA SAMMARTANO, GIORGIO SABELLA and OSCAR LISI Department of Biological, Geological and Environmental Sciences, Section of Animal Biology, University of Catania, Italy ABSTRACT A concise review of the articles about the origin of primordial germ cells (PGCs) in vertebrates is provided. Differences among various taxa concerning the origin of PGCs, not easily understandable on the base of traditional knowledge, are pointed out. All those differences can be explained taking into consideration the recent “theory of the endoderm as secondary layer” . That theory allows us to understand that those differences are only apparent, being related to modifications of stages of the consequent embryogeny, overall, to a different amount of yolk in the egg. Eggs very rich in yolk became meroblastic, and the portion of primordial ectomesenchyme destined to give rise to a part of the mesoderm and the PGCs separates early from the part destined to give rise to the rest of the mesoderm and to the digestive endoderm in order to form the vitel- line hypoblast lamina. To this lamina, in contrast to the traditional interpretation, a mesodermal, not endodermal, origin must be attributed. With the misunderstanding regarding the origin of this lamina clarified, all the differences about the origin of PGCs disappears. Furthermore, in taxa where PGCs were considered to be of endodermal origin, they too have a mesodermal origin. Considering that a mesodermal origin of PGCs has been demonstrated in all sponges and cnidarians, as well, a unique, mesodermal origin of germinal cells in all pluricellular animals results. KEY WORDS: vertebrate, primordial germ cell origin Introduction The origin and the migration of Primordial Germ Cells (PGCs) in vertebrates is an interesting, unsolved, problem. The gametes mature in the gonads but arise from PGCs, which appear in various sites, more or less far away from the area in which the gonadal anlagen will be formed, and reach their destination through blood or active migration. According to the literature, in some cases the PGCs arise from the mesoderm, in others from the endoderm or from the ectoderm; and in some cases they are even said to arise from extraembryonic areas. Even within the same class, they often seem to have different origins. This situation is, until now, diffcult to understand, and there is no interpretation from a phylogenetic point of view. Since the germinal cell surely became specialized in very primitive ances- tors, it is diffcult to suppose a different origin of the PGCs within the same phylum or the same class. In many cases it might appear more appropriate to use the words ectoblast, mesoblast and endoblast, but in this paper, when a precise distinction is not necessary, we will use the words ec- Int. J. Dev. Biol. 57: 809-819 (2013) doi: 10.1387/ijdb.120261gp www.intjdevbiol.com *Address correspondence to: Giovanni Pilato. Department of Biological, Geological and Environmental Sciences, section of Animal Biology, University of Catania, Via Androne 81, 95124 Catania, Italy. Tel: +39-095-730-6047. Fax: +39-095-32-7990. E-mail: pilato@unict.it Accepted: 13 May 2013. Final, author-corrected PDF published online: 19 February 2014. ISSN: Online 1696-3547, Print 0214-6282 © 2014 UBC Press Printed in Spain Abbreviations used in this paper: PGC, primordial germ cell. toderm, mesoderm and endoderm, as other authors do, to defne the germ layers. Historical review In the following historical excursus we start with the taxa showing situations which appear more primitive regarding the characteristics of the eggs and the frst stages of embryogenesis. For many years (Chiquoine, 1954), PGCs have been recog- nized as being larger than the surrounding cells, as possessing a prominent nucleolus, more darkly staining nuclear and plasma membrane and, overall, as having high alkaline phosphatase activity. Precursor cells of the PGCs, before showing alkaline phosphatase positivity, are recognized by the expression of the specifc markers Dazl and Vasa (Yoon et al., 1997; Bachvarova, 2009), or the transcriptional repressor Blmp1 detected in mice by Ohinata al. (2005).