Assistant Professor, Neurobiology University of Pittsburgh Email: monaghan@pitt.edu

Ph.D., Edinburgh University

Research Interests

Dr. Monaghan's laboratory is interested in defining the molecular and cellular mechanisms that determine cell fate in the central nervous system and how disruption of these events leads to behavioral abnormalities. Relatively few genes have been identified which control development of structures within the brain that are essential for emotion and cognition. Dr. Monaghan and colleagues have cloned a number of genes in mice that show a restricted pattern of expression in the developing brain. These genes code for transcription factors which are proposed to regulate key events in neurogenesis. Using genetic engineering, two of these genes, tailless and Spalt, have been mutated in mice. Tailless mutant animals exhibit profound behavioral abnormalities including, poor cognition, hyperexcitibility and severe aggressiveness. These abnormalities arise during development with changes in the rate of neuronal production in the limbic system. Spalt mutant animals do not feed and therefore die at birth. Spalt deficient animals have smaller cerebral hemispheres and olfactory bulbs. In the future this laboratory would like to use these animals to (1) analyze in more detail the developmental events at the molecular and cellular level that lead their respective phenotypes; (2) characterize the role of these genes in the development of the nervous system and define the specific molecular pathways disrupted in these animals; (3) create temporal and spatial conditional mutations in these genes in mice and decipher their anatomical and behavioral consequences; and (4) clone additional novel genes required for the formation/function of the mammalian brain.

Trainees have the opportunity to learn a variety of molecular and cellular techniques including gene cloning and characterization, genetic engineering in mice, production and handling of transgenic animals, embryology, gene manipulation in-vivo using in-utero electroporation, in vivo and in vitro cell culture and manipulation, immunohistochemistry, in situ hybridisation and analysis of behavior in mice.

Publications

• Land PW, Monaghan AP:  Abnormal development of zinc-containing cortical circuits in the absence of the transcription factor Tailless.  Brain Res Dev Brain Res 158(1-2): 97-101, 2005.

• Parrish M, Ott T, Lance-Jones C, Schuetz G, Schwaeger-Nickolenko A, Monaghan AP:  Loss of the mouse Sall3 gene leads to abnormalities in cranial nerves, palate deficiency and perinatal lethality. Mol Cell Biol 24(16): 7102-12, 2004.

• Roy K, Kuznicki K, Wu Q, Sun Z, Bock D, Schutz G, Vranich N, Monaghan AP:  The Tlx gene regulates the timing of neurogenesis in cortex.  J Neurosci 24(38): 8333-45, 2004.

• Land PW, Monaghan AP: Expression of the transcription factor, tailless, is required for formation of supervicial cortical layers.  Cereb Cortex 13(9): 921-31, 2003.

• Roy K, Thiels E, Monaghan AP:  Loss of the tailless gene affects forebrain development and emotional behavior.  Physiology and Behavior 77(4-5): 595-600, 2002.

• Monaghan AP, Kioschis P, Wu W, Zuniga A, Bock D, Poustka A, Delius H, Niehrs N.  Dickkopf genes are coordinately expressed in mesodermal lineages.  Mech Dev 1;87(1-2): 45-56, 1999.

• Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C:  Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391: 357-362, 1998.
• Monaghan AP, Bock D, Gass P, Lipp HP, Wolfer DP, Schwager A, Schutz G:  Aggressive behavior and defective limbic system in mice lacking the orphan nuclear receptor tailless.  Nature 390: 515-517, 1997.