Making Germ Cells from Human Embryonic Stem Cells - Male Germline Stem Cells Developmental and Regenerative Potential - page 59

Normal Human Testis DAZ -Deleted Testis

A

a b

B

RNA-binding domain DAZ repeat

DAZ

Y Chromosome

DAZL

Chromosome 3

BOULE

Chromosome 2

C

TESTIS

1 8
spermatocyte

2 8
spermatocyte

mature sperm

spermatid

spermatogonium

gonocyte

DAZ
DAZL

PGCs

BOULE

DAZ
DAZL

OVARY

antral follicle

1 8 oocyte 2 8 oocyte

oogonium mature ovum

ovulation

gonocyte

DAZL

Fig. 3.2 Genes of the DAZ family encode RNA-binding proteins that are involved in human germ
cell development and fertility. ( A ) Photomicrographs of hematoxylin and eosin stained cross-
sections of seminiferous tubules obtained from testicular biopsies from of: ( a ) a normal fertile man
showing normal spermatogenesis, and ( b ) a man with deletions of the DAZ genes showing a complete
loss of developing sperm or Sertoli cell-only syndrome ( Spg spermatogonia, Spc spermatocyte,
RSp round spermatid, Spd mature spermatid, MC myoid cell, SC Sertoli cell). ( B ) Schematic
representation of the human DAZ gene family including the DAZ , DAZL , and BOULE genes,
depicting their conserved RNA-binding domains and DAZ repeat elements. ( C ) A chronological
diagram of human gamete development from PGCs to mature sperm and oocytes, indicating the
sequence of expression of the three DAZ genes; genes are indicated in bold under the different
stages, with temporal gene expression indicated by arrows extending to the right

Xenopus , and the zebrafish Danio , the autosomal DAZ homolog Dazl encodes
components of the germ plasm (Houston and King 2000 ; Houston et al. 1998 ;
Maegawa et al. 1999 ; Mita and Yamashita 2000 ). In the frog Dazl is required for
embryonic germ cell production and migration (Houston and King 2000 ) and in the
zebrafish Dazl is expressed in primordial germ cells and developing gametes of the
testis and ovary (Maegawa et al. 1999 ). In mice, disruption of the Dazl gene results
in a loss of germ cells and complete absence of mature sperm and eggs and infertil-
ity in both males and females (Lin and Page 2005 ; Ruggiu et al. 1997 ; Lin et al.
2008 ; Saunders et al. 2003 ). Most evidence indicates that the sperm and eggs of