Page 38 - Mouse Molecular Genetics

Full Abstracts
Program number is above title. Author in bold is the presenter.
38
the absence of FGF4. Thus, Fgf4 mutant embryos initiated the PrE program but exhibited defects in its restriction phase, where
lineage bias is acquired. Consistent with this, XEN cells could be derived from Fgf4 mutant embryos in which PrE had been
restored and these cells appeared indistinguishable from wild-type cells. Interestingly, sustained exogenous FGF failed to rescue
the mutant phenotype. Instead, depending on concentration, we noted no effect, or conversion of all ICM cells to GATA6-
positive PrE. We therefore propose that heterogeneities in the availability of FGF produce the salt-and-pepper distribution of
lineage-biased cells.
12
Cell fate decisions regulating stem cell origins during preimplantation mouse development. Amy Ralston
1
,
Tristan Trum
1
,
Stephanie Blij
1
,
Chaoyang Wang
2
,
Paul Robson
2
,
Aytekin Akyol
3,4
,
Eric Fearon
3
,
Michael A. Halbisen
1
,
Yoshikazu Hirate
5
,
Hiroshi Sasaki
5
,
Tony Parenti
1
,
Eryn Wicklow
1
. 1)
Molecular, Cell, and Developmental Biology, UCSC, Santa Cruz, CA; 2)
Genome Institute of Singapore, Singapore; 3) Division of Molecular Medicine and Genetics, University of Michigan Medical
School; 4) Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey; 5) Department of Cell Fate
Control, Institute of Molecular Embryology and Genetics, Kumamoto University, Japan.
By studying mouse embryogenesis, we aim to discover how mammalian development is regulated and how embryonic stem
cells are created. Our approach is to examine the roles of stem cell factors in cell fate decisions in the mouse early embryo. Oct4
and Sox2 are essential regulators of pluripotency in embryonic stem cells, where they regulate each others expression. However,
we show that in the mouse blastocyst, these genes do not regulate each other, neither from the zygotic nor the maternal genome.
Rather, Oct4 and Sox2 regulate formation of the primitive endoderm, an extraembryonic tissue. Primitive endoderm cell fate is
thought to be induced by FGF signaling from the epiblast. We show that primitive endoderm development depends on Sox2,
acting upstream of FGF signaling from the epiblast, and Oct4, acting downstream of this signaling. In other words, Sox2
regulates primitive endoderm cell fate non cell-autonomously, while Oct4 regulates primitive endoderm fate cell-autonomously.
Finally, we examine stem cell factors thought to be required for trophectoderm, another extraembryonic lineage of the blastocyst.
Maternal Cdx2 and Sox2 are thought to be required for trophectoderm development. We use a genetic approach to delete Cdx2 in
the female germline and show that maternal Cdx2 is not required for mouse development. We also show that maternal Sox2 is
not required for TE fate. Rather, Sox2 expression is regulated by trophectoderm-specifying pathway upstream of Cdx2.
Ultimately, our data support a regulative, rather than deterministic, model of early mammalian development.
13
The T-box factor Eomesodermin is required in the visceral endoderm for proper axis specification in the early mouse
embryo. Sonja Nowotschin
1
,
Gloria Kwon
1
,
Evan Weiner
1
,
Anna Piliszek
1
,
Chai-an Mao
2
,
Kat Hadjantonakis
1
. 1)
Developmental Biology, Sloan-Kettering, New York, NY 10065, USA; 2) Department of Biochemistry and Molecular Biology,
University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Reciprocal inductive interactions between the epiblast and overlying visceral endoderm are critical for establishing the anterior-
posterior (AP) axis of the early mouse embryo. A first step in AP axis formation is the specification of a group of cells at the
distal tip of the egg cylinder, the distal visceral endoderm (DVE). The anterior transposition of this distal population of visceral
endoderm cells leads to the establishment of the AP axis.
Here we have examined the role of Eomesodermin (Eomes), a member of the T-box family of transcriptional regulators,
specifically within the visceral endoderm of the early embryo prior to AP axis formation. Our data demonstrate that Eomes is
required in the visceral endoderm for DVE specification, and that visceral endoderm tissue-specific ablation of Eomes results in
failure to establish the AP axis. Moreover, loss of Eomes in the visceral endoderm resulted in the upregulation of Nodal signaling
pathway components in the epiblast. AP patterning was restored when Nodal levels were reduced. These observations reveal a
pivotal role for Eomes, acting in the visceral endoderm to regulate the balance of Nodal signaling within the early post-
implantation mouse embryo.
14
How does retinoic acid regulate progenitor cell maintenance and differentiation in the nervous system and sensory
organs? Pascal Dolle
1*
,
Monika Rataj Baniowska
1
,
Muriel Rhinn
1
,
Wojciech Krezel
1
,
Karen Niederreither
2
,
Raj Ladher
3
,
Marie
Paschaki
1
. 1)
IGBMC, Strasbourg, France; 2) Dell Pediatric Research Institute, Austin, TX, USA; 3) RIKEN Center for
Developmental Biology, Kobe, Japan.
Retinoic acid (RA) has long been known to be a potent inducer of neuronal differentiation of various cell lines (including P19
or ES cells) or neural precursor cells during in vitro culture. Despite this fact, the in vivo function(s) of RA in cell populations
undergoing neurogenesis during development (the embryonic neuroepithelium giving rise to the brain and spinal cord, the
placodal epithelia giving rise to sensory neurons, etc) or adult life (e.g. the hippocampal neurons) remain largely debated. The
developing olfactory placode offers an interesting paradigm to study these events, as it gives rise to a population of sensory
neurons (the olfactory sensory neurons) that differentiate and become functional at perinatal stages, and have the capacity to
regenerate through life. Our studies using loss of function approaches in chicken and mouse indicate that RA is not required for
the initial inductive steps generating the olfactory placode. Instead, RA appears to promote generation of olfactory basal cells,
and prevent their progression into committed neuronal precursors. RA depletion results in a failure of progenitor maintenance and
consequently, due to this depletion, differentiation of olfactory neurons is not sustained. Furthermore, the regenerative capacity of
the olfactory epithelium in mutant mice deficient for RA synthesis is impaired. Our data suggest a mechanism by which local