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General Comment |
Deletions encompassing the Y chromosomal DAZ genes (deleted in azoospermia; 400003) are the most common molecularly
defined cause of infertility in humans. An array of 4 DAZ genes in 2 clusters is located on the Y chromosome and encodes
RNA-binding proteins with a common RNA recognition motif and a series of 8 to 18 DAZ repeats consisting of 24 amino acids
each that are rich in N, Y, and Q amino acid residues. DAZ homologs, identified in diverse organisms, are required for germ cell
development but differ in null phenotypes and expression patterns. In flies, disruption of the DAZ homolog 'Boule' causes male
meiotic arrest .
Using the yeast 2-hybrid system with a DAZ/DAZL construct as bait, Xu et al. (2001) identified an additional member of the
human DAZ gene family, BOULE. The protein encoded by human BOULE is more similar to Drosophila Boule than to
human DAZ or DAZL. The BOULE protein contains a single RNA binding domain with signature RNP1 and RNP2 repeats.
Extensive similarity is shared by the potential RNA binding domains of fly Boule, human BOULE, DAZ, and DAZL. The
protein predicted by a mouse Boule cDNA clone was 86% identical to human BOULE.
A Developmental Stage-Specific Switch from DAZL to BOLL Occurs during Fetal Oogenesis in Humans, but Not Mice. He J 2013 et al.
The Deleted in Azoospermia gene family encodes three germ cell-specific RNA-binding proteins (DAZ, DAZL and BOLL) that are essential for gametogenesis in diverse species. Targeted disruption of Boll in mice causes male-specific spermiogenic defects, but females are apparently fertile. Overexpression of human BOLL promotes the derivation of germ cell-like cells from genetically female (XX), but not male (XY) human ES cells however, suggesting a functional role for BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed during oogenesis in mammals also remains unclear. We have therefore investigated the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate that BOLL protein is expressed in the germ cells of the human fetal ovary, at a later developmental stage than, and almost mutually-exclusive to, the expression of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial follicles form, revealing BOLL expression to be restricted to a narrow window during fetal oogenesis. By quantifying the extent of co-expression of DAZL and BOLL with markers of meiosis, we show that this window likely corresponds to the later stages of meiotic prophase I. Finally, we demonstrate that Boll is also transiently expressed during oogenesis in the fetal mouse ovary, but is simultaneously co-expressed within the same germ cells as Dazl. These data reveal significant similarities and differences between the expression of BOLL homologues during oogenesis in humans and mice, and raise questions as to the validity of the Boll(-/-) mouse as a model for understanding BOLL function during human oogenesis.
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NCBI Summary:
This gene belongs to the DAZ gene family required for germ cell development. It encodes an RNA-binding protein which is more similar to Drosophila Boule than to human proteins encoded by genes DAZ (deleted in azoospermia) or DAZL (deleted in azoospermia-like). Loss of this gene function results in the absence of sperm in semen (azoospermia). Histological studies demonstrated that the primary defect is at the meiotic G2/M transition. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.
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Comment |
Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Kee K et al. The leading cause of infertility in men and women is quantitative and qualitative defects in human germ-cell (oocyte and sperm) development. Yet, it has not been possible to examine the unique developmental genetics of human germ-cell formation and differentiation owing to inaccessibility of germ cells during fetal development. Although several studies have shown that germ cells can be differentiated from mouse and human embryonic stem cells, human germ cells differentiated in these studies generally did not develop beyond the earliest stages. Here we used a germ-cell reporter to quantify and isolate primordial germ cells derived from both male and female human embryonic stem cells. By silencing and overexpressing genes that encode germ-cell-specific cytoplasmic RNA-binding proteins (not transcription factors), we modulated human germ-cell formation and developmental progression. We observed that human DAZL (deleted in azoospermia-like) functions in primordial germ-cell formation, whereas closely related genes DAZ and BOULE (also called BOLL) promote later stages of meiosis and development of haploid gametes. These results are significant to the generation of gametes for future basic science and potential clinical applications.
Mandon-Pepin B, et al 2003 reported the expression Profiles and Chromosomal Localization of Genes Controlling
Meiosis and Follicular Development in the Sheep Ovary.
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In female sheep fetuses, two of the most crucial stages of ovarian
development are prophase of meiosis I and follicle formation. In the
present study, sheep ovaries collected on Days 25, 38, 49, 56, 67, 75,
94, and 120 of gestation, at birth, and in adulthood were tested by
reverse transcription-polymerase chain reaction (RT-PCR) for the
expression of 14 genes known to be involved in the ovarian
differentiation in diverse organisms. The aim of this study was to
determine 1) the expression pattern of six genes involved in germ cell
development or meiosis (DMC1, SPO11, MSH4, MSH5, DAZL, and Boule) and
five ovary-derived factors (OVOL1, SIAH2, DIAPH2, FOXL2, and FGF9), 2)
the onset of gene expression for several members of the bone
morphogenetic protein (BMP) pathway involved in follicular development
(GDF9, BMP15, BMPR-IB), and 3) the chromosomal localization of seven of
these genes in the sheep genome. The RT-PCR analysis revealed that the
two germline-specific genes, DAZL and Boule, were expressed between 49
and 94 days postcoitum (dpc) with a similar pattern to typical meiosis
genes (DMC1, MSH4, and MSH5), suggesting their possible participation in
prophase of meiosis I. GDF9 and OVOL1 gene transcription started at 56
dpc and extended until birth, while BMP15 presented a more restricted
window of expression between 94 dpc and birth, corresponding to the
formation of first growing follicles. The homologous ovine genes for
SPO11, DMC1, MSH5, DAZL, FGF9, DIAPH2, and SIAH2 were located on OAR
13q21-22, 3q35, 20q22, 19q13, 10q15, Xq44, and 1q41-42, respectively. In
sheep, quantitative trait loci affecting female reproductive capacities
are currently being detected. The ontology and precise mapping of
ovarian genes will be useful to identify potential candidate genes that
might underlie these effects.
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