Tuesday, January 8, 2013
12:00 pm
Broad 100

Dev Bio SuperGroup Meeting

How does maternal infection perturb fetal brain development?
Wei-li Wu - Patterson Lab

Epidemiology studies identify maternal infection as a risk factor for autism and schizophrenia in the offspring.
To understand the mechanism of how maternal infection can alter fetal brain development, we use a mouse
model in which midgestation injection of the viral mimic poly(I:C) elicits maternal immune activation (MIA).
MIA offspring exhibit autistic- and schizophrenia-like behaviors as well as neuropathology characteristic of
these disorders. Prior work demonstrated that maternal interleukin-6 (IL-6) is a key cytokine that mediates
the effects of MIA on the fetus. To examine where maternal IL-6 acts, we are studying patterns of activation
of IL-6 signaling in the fetal brain. First, we demonstrate IL-6 increases in fetal brain at 3 hours following
maternal poly(I:C) injection. Second, we find that specific embryonic hindbrain regions respond to MIA -
phospho-STAT3 (pSTAT3) is elevated in rhombomeres 2 and 3. Third, analysis of the JAK/STAT signaling
pathway yields results consistent with the pSTAT3 immunostaining. The receptor for IL-6, IL-6Ra, is
expressed in brain regions associated with pathology in autism and schizophrenia. To examine the role of IL-
6 further, we are generating tissue-specific IL-6Ra knockout mice. The effects of MIA in these mice will be of
great interest.

Hierarchical progression of discrete regulatory states during organogenesis
Isabelle Peter - Davidson Lab

Mature organs consist of spatially organized compartments and cell types which express specific sets of
genes. Yet these cells often derive from a common field of precursor cells with homogenous gene
expression. What occurs during organogenesis therefore is that cells expressing the same combination of
transcription factors and signaling molecules, or a common regulatory state, are divided into an increasing
number of separate regulatory state domains. Each of these domains is specified by distinct regulatory
states which are expressed based on instructions encoded in gene regulatory networks. To address the
question of how regulatory state domains are formed during organogenesis, we are systematically analyzing
the spatial expression of most or hopefully all transcription factor genes which are required to establish the
spatial organization of the sea urchin embryonic gut. Comparison of expression patterns of currently about
50 transcription factor genes is used to map the regulatory state domains present in the mature gut. In
addition, we are determining the spatial expression of relevant transcription factors throughout the
development of the gut from its early precursor cells, which will reveal the hierarchical tree of cell fate
decisions responsible for establishing separate gene expression domains in the gut. For every cell fate
decision in this process, this project, once completed, will indicate both the earliest transcription factor gene
expressed in a new domain as well as the set of regulators which are possibly responsible for its control.
These results will thus provide a crucial entry point for the analysis of the regulatory network circuitry
underlying each cell fate decision. Ideas and work in progress will be presented.

Contact Julie Boucher jboucher@caltech.edu at 395-4952
For more information see Printable Flier
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