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Scott Weatherbee |
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| Assistant Professor |
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B.A. State University of New York, Oswego, 1993
Ph.D. University of Wisconsin, Madison, 1999
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| Research Interests: | |
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Limb development
Organogenesis
Mouse genetics
Integration of signaling pathways
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| Current Research: | |
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We use mice to study organogenesis during development, with a particular
emphasis on limb formation, patterning and growth. Limbs have played a crucial
role in animal evolution as the adaptive evolution of
vertebrates to aquatic, terrestrial, and aerial environments involved the
acquisition and modification of their limbs. Despite current knowledge
of the genes controlling patterning along the primary axes in the developing
limb, there are gaps in our understanding of how a limb is built.
For example, it is not known how earlyin
anterior-posterior or dorsal-ventral identity is imparted to the limb. There
is much to learn about the early stages of limb development and the
identification of new genes required for limb growth and patterning is needed.
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To broaden our insight into the genetic mechanisms underlying limb formation
and patterning I performed a forward genetics screen in the laboratories of
Kathryn Anderson and Lee Niswander in the mouse. Previous studies have shown
that forward genetics screens are feasible in the mouse and are an excellent,
unbiased method to uncover factors critical for a wide variety of
developmental processes. In a screen of ~100 pedigrees I identified three
recessive mouse mutants with defects in various aspects of limb development.
Two of these, hitchhiker and kerouac show preaxial polydactyly
and affect anterior-posterior patterning. In contrast, shorthand was
identified by defects in proximal-distal outgrowth of the limb. The genomic
regions linked to these mutants do not contain known limb patterning genes
indicating that we have identified novel genes required for limb development.
The characterization and cloning of the genes affected in these mutants should
provide a better understanding of anterior-posterior and proximal-distal
patterning during limb development.
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The lab is also continuing to work on a pair of mutants that were identified
in two independent screens. These mutants affect the low density lipoprotein
related 4 gene (Lrp4). Lrp4 is essential for proper patterning along all three
of the major axes during limb development. In addition, Lrp4 is required for
neuromuscular junction formation and normal development of ectodermal organs
such as mammary buds, teeth and vibrissae. We are interested in defining how
Lrp4 regulates the development of these vastly different organs and in
determining which signaling pathways Lrp4 interacts with.
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| Representative Publications: | |
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Weatherbee SD, Carroll SB. Selector genes and limb identity in arthropods and vertebrates. Cell 1999; 97:283-286.
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| Weatherbee SD, Niswander LA. Mechanisms of Chondrogenesis and Osteogenesis in Limbs, in Fins into Limbs: Evolution, Development, and Transformation. The University of Chicago Press, 2006.
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| Cretekos CJ, Weatherbee SD, Chen CH, Badwaik NK, Niswander LA, Behringer RR, and RasweilerIV JJ. Embryonic staging system for the short-tailed fruit bad Carollia perspicillata, a model organism for the mammalian order Chiroptera, based upon timed pregnancies in captive-bred animals. Developmental Dynamics 2005; 233:721-738
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| Weatherbee SD, Behringer RR, Rasweiler IV JJ and Niswander LA. Interdigital webbing retention in bat wings illustrates genetic changes underlying amniote limb diversification. PNAS 2006; 103:15103-15107.
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| Weatherbee SD, Anderson KV and Niswander LA. Ldl-receptor-related protein 4 is crucial for formation of the neuromuscular junction. Development 2006; 133:4993-5000.
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| Contact Information: | | |
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