Dr. Deborah Chapman

Genetics
K. Arndt
T.-L. Ashman
G. Campbell
D. Chapman
G. Hatfull
J. Hildebrand
L. Jacobson
S. Kalisz
J. Martens
W. Saunders
B. Stronach
S. Tonsor
R. Wood

Microbiology
J. Boyle
G. Hatfull
R. Hendrix
J. Lawrence
J. Pipas
M. Popa
R.L. Duda
S. Godfrey
V. Oke

Molecular Biology
K. Arndt
J. Franzen
P. Grabowski
G. Hatfull
R. Hendrix
L. Jen-Jacobson
J. Martens
C. Peebles
J. Pipas
J. Rosenberg
A. Schwacha
C. Walsh

Plant Biology
T.-L. Ashman
W. Carson
S. Kalisz
V. Oke
C. Partanen
S. Tonsor
B. Traw

Science Education
A. Bledsoe
K. Curto
L. Daniels
S. Godfrey
N. Kaufmann
C. LaFave
J. Newman
E. Polinko
M. Popa
L. Roberts
T. Seiflein
R. Sherwin
A. Slinskey Legg

Structural Biology
M. Grabe
J. Hempel
R. Hendrix
L. Jen-Jacobson
J. Rosenberg
A. VanDemark

Former Faculty

Photo of Dr.
Chapman

Mouse Developmental Biology

Associate Professor

Dr. Chapman received her Ph.D. in 1993 with Debra Wolgemuth at Columbia University, performed her postdoctoral studies with Virginia Papaioannou at Columbia University, and joined the Department in 1998.

Currently, Dr. Chapman is accepting graduate students in her laboratory. Dr. Chapman is accepting undergraduate researchers, and does sponsor students in other laboratories.

Professional Interests - Publications - Contact Information - Lab Personnel

Professional Interests of Deborah Chapman

Birth defects result from mistakes made during development of an organism from a single specialized cell, the fertilized egg, to a multicellular organismwith specialized tissues that function together. Normal development consists of carefully orchestrated events, many occurring simultaneously. The early events must be completed precisely for the later events to occur correctly. Therefore, changes in the developmental program can have dramatic effects on the organism as a whole. Sometimes the effects are so drastic that lethality occurs early in the development of the organism. Other times, the effects might not kill the developing organism, but may instead lead to devastating birth defects. An example of this is when the neural tube, the precursor to the central nervous system, fails to become fully enclosed within the vertebral column, resulting in spina bifida. Understanding how different developmental processes occur, specifically how individual genes affect these processes is the main interest of the Chapman lab.

The Chapman lab utilizes the mouse as an experimental system, taking advantage of the assets that the system has to offer, including its small size, genetics, transgenics and reverse genetics or gene targeting. With the sequencing of the human genome and the soon to be completed mouse genome, the ability to understand the function of all genes is becoming a reality. Because of the close relationship between the mouse and the human, it is possible to directly apply the things we learn in the mouse to the human.

During embryogenesis in animals the three germ layers, ectoderm, endoderm and mesoderm, are established during a process called gastrulation, which is characterized by extensive cell movement. The hallmark of gastrulation is the primitive streak - the source of mesoderm. Mesodermal cells emerge from the primitive streak and undergo regional changes to form the different types of mesoderm, including axial, paraxial, intermediate and lateral mesoderm. Paraxial mesoderm forms the somites, regularly spaced blocks of tissue that ultimately give rise to skeletal muscle, dermis, vertebrae and ribs (Fig. 1). Understanding how this mesodermal population is formed during development and the consequences that the failure to form this tissue has on development of the organism is one of the main goals of our laboratory. In its simplest form, failure to correctly form this tissue can lead to disruption of the axial skeleton (Fig. 2).

One gene that is essential for somite formation is Tbx6, which encodes a transcription factor. Like the homeobox genes, Tbx6 is a member of a large family of transcription factors - the T-box genes that are evolutionarily conserved from worms to humans. Tbx6 was implicated in the process of somitogenesis by its expression in the primitive streak and presomitic paraxial mesoderm during mouse embryogenesis (Chapman et al., 1996). Gene targeting in embryonic stem cells was used to make a specific mutation in the Tbx6 gene, which was later introduced back into mice. Characterization of these Tbx6 mutant embryos has led to a greater understanding of how this mesodermal cell population is established (Chapman and Papaioannou, 1998). Although irregular somites form in the neck region of Tbx6 mutant embryos, more posterior paraxial tissue does not form somites, but instead differentiates along a neural pathway, forming neural tube-like structures flanking the axial neural tube (Fig. 3). Posterior tissue expresses primitive streak markers, but does not express markers of presomitic paraxial mesoderm. Results from these studies indicate that Tbx6 is essential for the specification of posterior paraxial mesoderm and that in its absence, cells destined to form posterior somites differentiate along a neural pathway.

Figure 1. Mouse embryo

Figure 2. Mouse skeletons

Figure 3. Mouse mutants

To understand how paraxial mesoderm is established, we are using a combination of mouse transgenic technology, experimental embryology and molecular biology. As demonstrated by the mutational studies, Tbx6 is a key player in this process. We are therefore attempting to identify the genes functioning both upstream and downstream of this transcription factor. To identify genes directly upstream of Tbx6, we are taking a transgenic approach to identify the regulatory regions required for directing the correct spatial and temporal expression of Tbx6 during development. This approach involves the generation of reporter constructs, consisting of genomic fragments from the Tbx6 locus cloned upstream of a lacZ reporter gene. Constructs capable of directing the expression of the lacZ gene in a Tbx6-specific pattern in transgenic embryos can then be further analyzed in a variety of ways. Because the regulatory elements controlling Tbx6 expression are likely to be conserved between species, in particular the mouse and human, comparisons can be made between the genes to identify these conserved sequence elements . In addition, deletion studies of the transgene can be performed to delimit the region of interest and eventually analyze the smaller regions for potential transcription factor binding sites. Since Tbx6 itself encodes a transcription factor, we are using differential screens to identify both direct and indirect targets of Tbx6. By using this multi-faceted approach, we hope to uncover the genetic and molecular mechanisms underlying the establishment of paraxial mesoderm and ultimately the somites in the mouse and then to then use this information to investigate human birth defects.

Publication Archive
26 Citations
22 Abstracts
16 PDFs

Recent Publications of Deborah Chapman

Wehn, A.K., P.H. Gallo, and D.L. Chapman (2009) Generation of transgenic mice expressing Cre recombinase under the control of the Dll1 mesoderm enhancer element. Genesis 47:309-313

Farkas, D.R., and D.L. Chapman (2009) Kinked tail mutation results in notochord defects in heterozygotes and distal visceral endoderm defects in homozygotes. Dev Dyn 0:

Oginuma, M., Y. Niwa, D.L. Chapman, and Y. Saga (2008) Mesp2 and Tbx6 cooperatively create periodic patterns coupled with the clock machinery during mouse somitogenesis. Development 135:2555-2562

Chapman, D.L. (2006) Paraxial mesoderm signals are required for intermediate mesoderm formation in the mouse. Dev. Biol. 295:393-394 (PDF Reprint: 87 kb)

White, P.H., D.R. Farkas, and D.L. Chapman (2005) Regulation of Tbx6 expression by Notch signaling. Genesis 42:61-70 (PDF Reprint: 703 kb)

White, P.H., and D.L. Chapman (2005) Dll1 is a downstream target of Tbx6 in the paraxial mesoderm. Genesis 42:193-202 (PDF Reprint: 557 kb)

Hogan, K.A., C.A. Ambler, D.L. Chapman, and V.L. Bautch (2004) The neural tube patterns vessels developmentally using the VEGF signaling pathway. Development 131:1503-1513 (PDF Reprint: 1.6 MB)

Chapman, D.L., A. Cooper-Morgan, Z. Harrelson, and V.E. Papaioannou (2003) Critical role for Tbx6 in mesoderm specification in the mouse. Mech. Develop. 120:837-847 (PDF Reprint: 547 kb)

White, P.H., D.R. Farkas, E.E. McFadden, and D.L. Chapman (2003) Defective somite patterning in mouse embryos with reduced levels of Tbx6. Development 130:1681-1690 (PDF Reprint: 396 kb)

Maeda, T., D.L. Chapman, and A.F. Stewart (2002) Mammalian vestigial-like 2, a cofactor of TEF-1 and MEF2 transcription factors that promotes skeletal muscle differentiation. J. Biol. Chem. 277:48889-48898 (PDF Reprint: 624 kb)

Xue, Y., X. Wang, Z. Li, N. Gotoh, D.L. Chapman, and E.Y. Skolnik (2001) Mesodermal patterning defect in mice lacking the Ste20 NCK interacting kinase (NIK). Development 128:1559-1572 (PDF Reprint: 529 kb)

How to Contact Deborah Chapman

US Mail
University of Pittsburgh
Department of Biological Sciences
101A Life Sciences Annex
4249 Fifth Avenue
Pittsburgh, PA 15260

Phone, FAX, Internet
Office : (412) 624-0774
Lab : (412) 624-0580
FAX : (412) 624-4759
Email : dlc7+@pitt.edu
Web :

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