THE 2012 GSA HONORS AND AWAR DS
The 2012 Thomas Hunt Morgan Medal
Kathryn V. Anderson
The Genetics Society of America annually honors members who have made outstanding contributions to genetics. The Thomas Hunt
Morgan Medal recognizes a lifetime contribution to the science of genetics. The Genetics Society of America Medal recognizes particularly
outstanding contributions to the science of genetics over the past 31 years. The George W. Beadle Medal recognizes distinguished service
to the field of genetics and the community of geneticists. The Elizabeth W. Jones Award for Excellence in Education recognizes individuals
or groups who have had a significant, sustained impact on genetics education at any level, from kindergarten through graduate school
and beyond. The Novitski Prize recognizes an extraordinary level of creativity and intellectual ingenuity in solving significant problems in
biological research through the application of genetic methods. We are pleased to announce the 2012 awards.
I
T is a pleasure to congratulate Kathryn Anderson on her
selection as the recipient of the 2012 Thomas Hunt Morgan
Medal from the Genetics Society of America. Kathryn was
chosen as this year’s recipient because of her career-long
record of using elegant unbiased genetic screening and
mutant/transgenic analysis to attack and solve important
questions in developmental genetics. She is best known for
three areas of work.
The genetics of early embryogenesis in Drosophila
Kathryn began her studies of genes that regulate development when she was a graduate student with Judy Lengyel
at the University of California at Los Angeles. Her graduate
work established that the early Drosophila embryo’s development is largely under the control of maternally provided
products, with a switchover to largely zygotic control after
2 hr of development (Anderson and Lengyel 1980). Subsequently, as a postdoc with Christiane Nüsslein-Volhard
at the Max Planck Institut at Tübingen, and then continuing
as an independent investigator at the University of California, Berkeley, Kathryn uncovered and dissected the maternal
protein cascade that determines the dorsoventral polarity of
the Drosophila embryo (e.g., Anderson and Nüsslein-Volhard
1984; reviewed in Morisato and Anderson 1995). Kathryn
and her lab made numerous groundbreaking advances, of
which a few are enumerated here. She showed that Toll was
an important mediator of dorsoventral polarity (Anderson
et al. 1985b) and that a ventral side developed locally, where
Copyright © 2012 by the Genetics Society of America
doi: 10.1534/genetics.112.139030
Toll was active (Anderson et al. 1985a). Her lab then reported that Toll was a membrane protein that resembled
a class of transmembrane receptors that included the interleukin-1 receptor (Hashimoto et al. 1988). This finding was
quite surprising, given that Toll was active in regulating an
embryo enclosed in an eggshell without any obvious cells
signaling to it! As is characteristic of Kathryn’s work, however, every possible alternative had been checked and eliminated, and there was no question that her iconoclastic
finding was correct. To uncover what activated this receptor,
Kathryn’s lab was a major contributor in determining the
cascade of maternal dorsoventral (D/V) genes, sorting them
into those that acted up- or downstream of Toll. Among the
upstream genes, Kathryn’s lab identified members of a protease cascade (e.g., Chasan et al. 1992; reviewed in Hecht
and Anderson 1992) present in the perivitelline space outside
the egg’s plasma membrane and, through meticulous genetic analysis, identified the ultimate, maternally provided target of that cascade as the product of the spätzle
gene (Schneider et al. 1994). The genetic and biochemical
experiments of Kathryn’s lab showed that spätzle was the
ligand for Toll. In separate experiments, her lab showed
that the BMP-family member dpp acted zygotically, after
the maternal cascade, as a morphogen to determine dorsality (Ferguson and Anderson 1992). Kathryn’s articles
are classics, distinguished not only by their importance
but also by the elegance of their genetic analysis—in experimental design, compelling results, and incisive interpretation; they are wonderful exemplars for students, for
example, and many textbooks devote large parts of chapters
to work from her lab.
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June 2012
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The genetics of the Toll pathway in immunity
It turned out that Toll had a role beyond D/V determination—
a role more consistent with its membership in the interleukin-1
receptor family: Toll is an important receptor in the immunity cascade in Drosophila (reviewed in Anderson 2000).
The genetic analysis of the Toll pathway in the fly embryo
laid the foundation for identifying and characterizing the
roles of Toll-like receptors in innate immunity in mammals.
Kathryn applied the genetic tools that she had developed for
the analysis of D/V patterning to dissect the pathways in
which Toll functioned to transduce immunity signals, working them out in detail by systematic genetic screens. Her
work uncovered unanticipated and important players in
the immunity cascade, including the identification of a peptidoglycan recognition protein as a key activator of antimicrobial peptide responses (Choe et al. 2002).
The genetics of early embryogenesis in mice
About 15 years ago, first at the University of California at
Berkeley and then at Sloan-Kettering, Kathryn courageously
began an entirely new project. She chose to apply to the
mouse the same type of unbiased genetic screening that had
been so powerful in identifying new genes and cascades in
Drosophila development (Kasarskis et al. 1998). Although of
undisputed importance, such a screen was clearly going to
take a long time to pay off. Recognizing that such a screen
was, nevertheless, essential for a true understanding of the
genes that controlled mouse embryogenesis, Kathryn began by doing a sabbatical with Rosa Beddington to begin
to learn mouse embryology. Then, in her own lab, she
forged ahead with the same experimental care, rigor, and
creative experimental design that characterized her fly
work. Kathryn is one of the few established fly researchers
to make a complete transition to the mouse. Her screen has
generated .130 mutants that affect the mid-gestational
mouse embryo, and Kathryn and her collaborators have
molecularly identified the mutant lesions in nearly 90 of
these genes. These mutants allow delineation of pathways
by which the mouse embryo’s body axes are established or
that regulate morphogenesis, topics that resonate with
Kathryn’s earlier work on Drosophila embryos. Results of
Kathryn’s unbiased screens have led to the identification of
morphogenesis regulators at many biological levels, including transcription, actin branching, vesicle transport, and
collective cell migration (to name just a few; e.g., see
Eggenschwiler et al. 2001; Merrill et al. 2004; Rakeman
and Anderson 2006; Migeotte et al. 2011). The discoveries
have taken the field into new directions or connected
known pathways or phenomena in previously unanticipated ways. For example, results from Kathryn’s screens
revealed an unanticipated essential role of cilia in hedgehog signaling during early mouse embryogenesis. Because
two of the genes identified in the screens had homologs
that are important in intraflagellar transport in Chlamydo-
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Honors and Awards
monas, Kathryn examined cilia in the mutant embryos
(Huangfu et al. 2003). She found that cilia were absent
from the node in the mutants. Given the role of cilia in
setting up left/right (L/R) polarity, loss of cilia from the
node would be expected to cause L/R patterning defects,
and Kathryn’s lab observed just such effects in the mutants.
Kathryn’s careful phenotyping showed that the same
mutants’ neural defects also resembled those of SHH
mutants. This led her to make the leap to test the relationship of hedgehog pathway members to cilia. Kathryn and
her lab showed that hedgehog pathway components are
localized to, or enriched in, cilia and that hedgehog signaling itself can affect this localization. From there, she
and her lab branched out to dissect node assembly, ciliary
assembly and intracilia transport, the hedgehog pathway’s
role in development, and disease-associated genes that
affect ciliary structure or formation (e.g., Caspary et al.
2007; Tuson et al. 2011), while continuing to dissect other
pathways that regulate morphogenesis and patterning of
the body.
Kathryn is a developmental-geneticist’s geneticist. From
first principles, she designs and does rigorous large-scale
unbiased screens for the genes that regulate important developmental processes. Her great attention to detail, sophisticated genetic manipulations (every type of epistasis,
molecular genetic design, etc.), and creative genetic and
molecular thought has repeatedly led to major, important,
and unanticipated discoveries of new developmental and
biological principles. And she has done this in two model
organisms. In addition to her major scientific contributions,
Kathryn is a collaborative and supportive scientist who generously shares reagents and mutants with the community.
She works quietly, but the importance and quality of her
work speaks for itself and has already led to several recognitions, including Kathryn’s election as a Fellow of the National Academy of Sciences, the American Association for
the Advancement of Science, and the American Academy of
Arts and Sciences. Kathryn modestly credits her mentors,
all outstanding women scientists, with helping her succeed.
She, in turn, has trained and mentored many geneticists
who themselves have gone on to make major contributions
to the fly and mouse fields. We are delighted that the Genetics Society of America has chosen to recognize, with this
medal, Kathryn’s career-long record of important and precedent-setting discoveries based on elegant genetics.
Literature Cited
Anderson, K. V., 2000 Toll signaling pathways in the innate immune response. Curr. Opin. Immunol. 12: 13–19.
Anderson, K. V., and J. A. Lengyel, 1980 Changing rates of histone mRNA synthesis and turnover in Drosophila embryos. Cell
21: 717–727.
Anderson, K. V., and C. Nüsslein-Volhard, 1984 Information for
the dorsal–ventral pattern of the Drosophila embryo is stored as
maternal mRNA. Nature 311: 223–227.
Anderson, K. V., L. Bokla, and C. Nüsslein-Volhard, 1985a Establishment of dorsal-ventral polarity in the Drosophila embryo:
the induction of polarity by the Toll gene product. Cell 42:
791–798.
Anderson, K. V., G. Jurgens, and C. Nüsslein-Volhard, 1985b Establishment of dorsal-ventral polarity in the Drosophila embryo:
genetic studies on the role of the Toll gene product. Cell 42:
779–789.
Caspary, T., C. E. Larkins, and K. V. Anderson, 2007 The graded
response to Sonic Hedgehog depends on cilia architecture. Dev.
Cell 12: 767–778.
Chasan, R., Y. Jin, and K. V. Anderson, 1992 Activation of the
easter zymogen is regulated by five other genes to define
dorsal-ventral polarity in the Drosophila embryo. Development 115: 607–616.
Choe, K. M., T. Werner, S. Stoven, D. Hultmark, and K. V. Anderson,
2002 Requirement for a peptidoglycan recognition protein
(PGRP) in Relish activation and antibacterial immune responses
in Drosophila. Science 296: 359–362.
Eggenschwiler, J. T., E. Espinoza, and K. V. Anderson, 2001 Rab23
is an essential negative regulator of the mouse Sonic hedgehog
signalling pathway. Nature 412: 194–198.
Ferguson, E. L., and K. V. Anderson, 1992 Decapentaplegic acts as
a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. Cell 71: 451–461.
Hashimoto, C., K. L. Hudson, and K. V. Anderson, 1988 The Toll
gene of Drosophila, required for dorsal-ventral embryonic polarity,
appears to encode a transmembrane protein. Cell 52: 269–279.
Hecht, P. M., and K. V. Anderson, 1992 Extracellular proteases and
embryonic pattern formation. Trends Cell Biol. 2: 197–202.
Huangfu, D., A. Liu, A. S. Rakeman, N. S. Murcia, L. Niswander
et al., 2003 Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426: 83–87.
Kasarskis, A., K. Manova, and K. V. Anderson, 1998 A phenotypebased screen for embryonic lethal mutations in the mouse. Proc.
Natl. Acad. Sci. USA 95: 7485–7490.
Merrill, B. J., H. A. Pasolli, L. Polak, M. Rendl, M. J. Garcia-Garcia
et al., 2004 Tcf3: a transcriptional regulator of axis induction
in the early embryo. Development 131: 263–274.
Migeotte, I., T. Omelchenko, A. Hall, and K. V. Anderson,
2011 Rac1-dependent collective cell migration is required for
specification of the anterior-posterior body axis of the mouse.
PLoS Biol. 8: e1000442.
Morisato, D., and K. V. Anderson, 1995 Signaling pathways that
establish the dorsal-ventral pattern of the Drosophila embryo.
Annu. Rev. Genet. 29: 371–399.
Rakeman, A. S., and K. V. Anderson, 2006 Axis specification and
morphogenesis in the mouse embryo require Nap1, a regulator of
WAVE-mediated actin branching. Development 133: 3075–3083.
Schneider, D. S., Y. Jin, D. Morisato, and K. V. Anderson, 1994 A
processed form of the Spätzle protein defines dorsal-ventral polarity in the Drosophila embryo. Development 120: 1243–1250.
Tuson, M., M. He, and K. V. Anderson, 2011 Protein kinase A acts
at the basal body of the primary cilium to prevent Gli2 activation
and ventralization of the mouse neural tube. Development 138:
4921–4930.
Mariana F. Wolfner and Tim Schedl
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