Abstracts - Society for Developmental Biology

116
Program/Abstract # 351
Roles of Noggin, a BMP antagonist, in development of craniofacial skeletal elements
Matsui, Maiko; Klingensmith, John, Duke University, Durham, United States
The mammalian craniofacial skeleton consists of more than twenty small bones and cartilages that are formed precisely
during development to create functional structures - the face and the head. However there exist known deformities in the
mammalian craniofacial skeletal structures. For example, cleft palate and cleft lip are the most common craniofacial
defects in human newborns. Micrognathia, which is characterized bymandibular hypoplasia, is another example of
common congenital malformation. Yet, the causes of these defects remain incompletely understood. It is critical to study
mechanisms of proper craniofacial development. Previously, mice lacking the Bone Morphogenetic Protein (BMP)
antagonist Noggin exhibit a whole spectrum of craniofacial defects including fully penetrant primary and secondary cleft
palate and micrognathia. Noggin is expressed in multiple domains during the important period of craniofacial
development. Different domains of Noggin expressed may cooperate to tune appropriate BMP signaling gradient within
these domains as well as surrounding tissues for proper morphogenesis. In this study, we employed tissue specific
inactivation of Noggin to address the roles of Noggin in neural crest cells (NCCs) for craniofacial skeletogenesis.
Interestingly, our data indicate that Noggin in NCCs plays an important role in NCC-derived tissues as well as in the
nonNCC-derived tissues. We also tested if Noggin in NCCs has anon-autonomous role against BMPs in the neighboring
mesoderm-derived tissues by overactivating BMP signaling only in NCCs. All together, our results suggest that Noggin in
NCCs plays a critical role to regulate patterning and growth of both NCC- and mesoderm-derived craniofacial
skeletogenesis.
Program/Abstract # 352
Effects of Methoxychlor (MXC) on expression of SOX9/WNT4 genes in development of the male reproductive
system
Soo Jung, Park; Sung Won, Kim; Cheol Ho, Park; You Jin, Hwang; Dae Young, Kim, Gachon University of Medicine and
Science, Incheon, Republic of Korea
Methoxychlor (MXC) is an organochlorine pesticide that alternated DDT because of high toxic reason. MXC, one of
estrogenic endocrine disrupting chemicals (EDCs), has been proved to have an adverse effect on developing male
reproductive system according to recent researches. MXC has an anti-androgenic effect that reduces testosterone binding
sites of androgen receptors. Therefore we studied how MXC can affect embryonic male reproductive system to verify the
effect of MXC in a pregnancy period. The chemical was applied 100 mg/kg dose by gavage daily to pregnant mouse and
the control group was treated with just sesame oil in same dose of MXC. After embryonic sex differentiation was finished,
we took out the embryos to identify the differences between MXC and control groups. We measured SOX9 and WNT4
gene expression with reverse transcription polymerase chain reaction (RT-PCR). In case of SOX9 gene, this begins the
cascade reaction of testis morphogenesis. The other, WNT4, is expressed in both male and female although after sex
determination, this is involved in just ovary morphogenesis. Exploiting some of embryos, androgen receptors in testis was
quantified by western blot and others were detected with immunohistochemistry to analyze the morphological differences
in reproductive system in both groups. Through this study, we confirmed the difference of gene expression between in both
groups so as the androgen receptors either. Therefore we could understand how embryonic reproductive system got
affected by MXC.
Program/Abstract # 353
Retinoic acid role in forelimb initiation is mediated by repression of axial FGF signaling
Cunningham, Thomas J., Sanford-Burnham Med Research Institute Development and Aging, La Jolla, United States;
Sandell, Lisa (Louisville, KY, United States); Evans, Silvia (La Jolla, United States); Trainor, Paul (Kansas City, MO,
United States); Duester, Gregg (La Jolla, CA, United States)
Prior to limb budding, retinoic acid (RA) is required to initiate the forelimb fieldin both mouse and zebrafish. Loss of the
forelimb bud during RA deficiency hasbeen proposed to be secondary to enlargement of the adjacent heart which expands
due to ectopic cardiac FGF signaling. Previous studies on Raldh2-/- embryos completely lacking RA synthesis
demonstrated absent forelimbs and enlargement of the heart, associated with ectopic expression of Fgf8 in the heart and
caudal progenitor zone resulting in expansion of FGF signaling throughout the trunk. Here, we show that Rdh10 mutants
exhibit stunted forelimbs (rather than complete loss) and enlarged hearts. Rdh10 mutants exhibit loss of heart RA activity
but maintain caudal progenitor zone RA activity. Accordingly, Fgf8 expression in the heart is expanded posteriorly, while
Fgf8 in the caudal progenitor zone appears normal. Thus, Rdh10 mutants differ from Raldh2 mutants in that FGF signaling
does not expand anteriorly from the caudal progenitor zone, which we suggest is permissive for forelimb initiation, albeit