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Early development of the forebrain and pituitary in mice
The elaboration of the embryonic body plan and the commitment of undifferentiated embryonic cells to specific developmental
pathways are the two most defining features of vertebrate development. Conserved transcription factors, such as those encoded
by homeobox genes, play key roles in regulating both processes. Our laboratory has identified several homeobox gene family
members that are involved in these early determinative events in embryogenesis. We are utilizing a combination approaches,
including molecular biology, experimental embryology, gene transfer technology, in situ hybridization, and genetics to
study their regulation and function in the mouse embryo.
A major focus of the laboratory is on the development of the forebrain and pituitary. The Rpx gene is expressed
sequentially from the onset of gastrulation in the anteriormost endoderm, prechordal plate, and anterior neural plate.
At later stages of development it is expressed in Rathke's pouch, the primordium of the anterior and intermediate lobes of
the pituitary. We have shown that Rpx plays an important role in the initial determination and differentiation
of the neural plate and pituitary by generating both gain-of-function and loss-of-function mouse models using transgenic and
embryonic stem (ES) cell technology, respectively. In a broader context, Rpx is a component of a regulatory
network involved in pituitary organogenesis. Our studies of Rpx function and regulation serve as a launching point
for understanding this intrinsic genetic program on the molecular level
We have defined critical regulatory elements required for proper expression of Rpx in transgenic embryos as a
first step in defining other genes, both upstream and downstream of Rpx, in the regulatory hierarchy governing
forebrain and pituitary development. We have also developed an in vitro tissue explant system to molecularly dissect
the inductive interactions required for the establishment of the hypothalamic-pituitary axis during development.
Selected Publications
Hermesz E, Mackem S, Mahon KA (1996) Rpx: a novel anterior-restricted homeobox gene
progressively activated in the prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo.
Development 122:41-52.
Sheng HZ, Zhadanov AB, Mosinger B Jr, Fujii T, Bertuzzi S, Grinberg A, Lee EJ, Huang SP, Mahon KA,
Westphal H (1996) Specification of pituitary cell lineages by the LIM homeobox gene Lhx3. Science
272:1004-1007.
Gage PJ, Brinkmeier ML, Scarlett LM, Knapp LT, Camper SA, Mahon KA (1996) The Ames dwarf gene, df,
is required early in pituitary ontogeny for the extinction of Rpx transcription and initiation of
lineage-specific cell proliferation. Molecular Endocrinology 10:1570-1581.
Sheng HZ, Moriyama K, Yamashita T, Li H, Potter SS, Mahon KA, Westphal H (1997) Multistep control of
pituitary organogenesis. Science 278:1809-1812.
Kos L, Chiang C, Mahon KA (1998) Mediolateral patterning of somites: multiple axial signals, including
Sonic hedgehog, regulate Nkx-3.1 expression. Mechanisms of Development 70:25-34.
Takuma N, Sheng HZ, Furuta Y, Ward JM, Sharma K, Hogan BL, Pfaff SL, Westphal H, Kimura S, Mahon KA (1998)
Formation of Rathke's pouch requires dual induction from the diencephalon. Development 125:4835-4840.
Morasso MI, Grinberg A, Robinson G, Sargent TD, Mahon KA (1999) Placental failure in mice lacking the
homeobox gene Dlx3. Proceedings of the National Academy of Sciences U.S.A. 96:162-167.
Hermesz E, Williams-Simons L, Mahon KA (2003) A novel inducible element, activated by contact with
Rathke's pouch, is present in the regulatory region of the Rpx/Hesx1 homeobox gene. Developmental
Biology 260:68-78.
Contact Information
- Kathleen A. Mahon, Ph.D.
- Department of Molecular and Cellular Biology
- Baylor College of Medicine
- One Baylor Plaza M804
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-5550
- Fax: (713) 790-0545
- E-mail: kmahon@bcm.tmc.edu
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