Congress Abstracts - Society for Developmental Biology

opposed roles during early gastrulation. We propose that ADMP has a very early dorsal function promoting the expansion of the
organizer domain and subsequently, it contributes to the BMP gradient to restrict the organizer. These opposed ADMP activities scale
the organizer domain and the BMP gradient with embryo size.
Program/Abstract # 27
Stromal-epithelilal crosstalk regulates nephron progenitor cell fate
Amrita Das (UT Southwestern, USA)
The kidney is an essential organ that regulates the chemistry of the blood. It is composed of numerous epithelial tubules known as
nephrons. For years, it has been believed that the development of a nephron was soleley dependent upon reciprocal interactions
between two embryonic populations, the ureteric bud epithelia and the metanephric mesenchyme. Signals from the mesenchyme
promote branching morphogenesis of the bud, while signals from the bud regulate the survival and renewal of a progenitor population
within the mesenchyme. The bud also induces a sub-population of the progenitors to undergo a mesenchymal-to-epithelial transition
(MET) and differentiate into an epithelial tubule that will form the nephron. We found that Wnt9b, a ureteric bud-derived signal, was
necessary for both mesenchymal progenitor renewal and epithelial differentiation. How the same molecule induced two seemingly
contradictory processes was unknown. Here, we show that signals from the overlying stromal fibroblasts modify Wnt9b activity
promoting progenitor cell differentiation. The atypical cadherin Fat4, encodes at least a part of this stromal signal. Fat4 acts by
promoting the removal of the transcriptional regulators Yap and Taz from the nucleus. Nuclear Taz/Yap cooperate with beta-catenin
to promote progenitor renewal and repress differentiation. Thus, we have found that opposing signals (Wnt9b from the ureteric bud
and Fat4 from the stroma) cooperate to regulate progenitor cell renewal and differentiation. Proper balancing of these signals is
required to assure the proper number of nephrons form assuring optimal kidney function.
Program/Abstract # 28
Regulation of Hippo signaling by MAPK pathways
Kenneth Irvine, Venu Reddy, Gongping Sun, Veronica Codelia (HHMI/Rutgers, USA)
The Hippo pathway regulates organ growth; defining mechanisms that regulate this pathway is crucial to understanding how it is
utilized to control growth in different contexts. In earlier work we have characterized some of the key upstream regulators of Hippo
signaling in Drosophila, such as Fat, Expanded, and Merlin. More recently, we have begun to identify and characterize additional
inputs into Hippo pathway regulation. Epidermal Growth Factor Receptor (EGFR) signaling plays an important role in growth control,
and inappropriate activation of EGFR signaling has been implicated in several cancers. We have identified and characterized a
conserved link between EGFR and Hippo signaling pathways. EGFR activates the Hippo pathway transcription factor Yorkie (Yki)
through the Ras-MAPK branch of EGFR signaling. Genetic and biochemical experiments implicate the Ajuba LIM protein Jub as a
key target of EGFR-Ras-MAPK signaling within the Hippo pathway. An EGFR-Hippo pathway link is conserved in mammalian cells.
Wounding, apoptosis or infection can trigger a proliferative response in neighboring cells to replace damaged tissue. Studies in
Drosophila have implicated Jun kinase (JNK)-dependent activation of Yki as essential to regeneration-associated growth, as well as
growth associated with neoplastic tumors. We have found that JNK regulation of Hippo signaling is conserved in mammalian cells,
and identified a conserved molecular mechanism by which JNK impinges on Hippo signaling, and which is distinct from EGFR-Ras-
MAPK regulation of Hippo signaling.
Program/Abstract # 29
Coordination of patterning and growth in the spinal cord
Anna Kicheva, Ana Ribeiro, Helena Perez Valle, James Briscoe (NIMR, UK)
In the developing spinal cord, several types of neuronal progenitors are specified and spatially arranged along the dorso-ventral axis in
response to the morphogen gradient of Sonic hedgehog (Shh). This process of establishment of the neural tube pattern involves the
transcriptional specification of progenitor identity, as well as proliferation and terminal differentiation. How these processes are
coordinated is poorly understood. To address this problem, we measured the three-dimensional growth rates of each gene expression
domain in mouse and chick neural tubes during 3 days of development using immunostainings of sections, clonal analysis, and
photoconversion experiments. Independent measurements of the rates of proliferation and differentiation showed that these processes
alone can account for the size changes of the gene expression domains for most of the experimental time period. Consistent with this,
Olig2 lineage tracing experiments at different developmental stages show that changes of cell identity occur rarely later in
development. Our data suggests a 2-phase model of patterning: early domain size depends on switches of cell identity, which are
instructed by Shh signaling, whereas the late elaboration of pattern depends on proliferation and differentiation. We are validating this
model using different conditions where growth or signaling is altered.
Program/Abstract # 30
From deep water to deep learning: Modeling the teratogenic impacts of the Deepwater Horizon oil spill
Michael Barresi (Smith, USA)
Deep learning in a laboratory course that fosters cross-disciplinary comprehension of key concepts, confidence in experimental design
and implementation, and development of critical thinking skills is challenging to achieve. However, engaging students with a novel
and relevant research question can reap tangible rewards. The Deepwater Horizon disaster is the largest marine oil spill in history, and
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