Genetic analysis of vertebrate CNS development

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 restricted patterns 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 recently been mutated in mice. Tailless mutant animals exhibit profound behavioral abnormalities including poor cognition, hyperexcitibility, and severe aggressiveness. Spalt mutant animals do not feed and therefore die perinatally. 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 roles of these genes in the development of the nervous system and define the specific molecular pathways disrupted in these animals; (3) create temporally and spatially regulated conditional mutations in mice and decipher their anatomical and behavioral consequences, and, (4) clone additional novel genes required for the formation/function of the mammalian brain.

Sample Publications:

Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome.
Harrison SJ, Nishinakamura R, Jones KR, Monaghan AP.
Dis Model Mech. 2012 Jan 25.

Comprehensive polyadenylation site maps in yeast and human reveal pervasive alternative polyadenylation.
Ozsolak F, Kapranov P, Foissac S, Kim SW, Fishilevich E, Monaghan AP, John B, Milos PM.
Cell. 2010 Dec 10;143(6):1018-29.

New class of gene-termini-associated human RNAs suggests a novel RNA copying mechanism.
Kapranov P, Ozsolak F, Kim SW, Foissac S, Lipson D, Hart C, Roels S, Borel C, Antonarakis SE, Monaghan AP, John B, Milos PM.
Nature. 2010 Jul 29;466(7306):642-6.

A sensitive non-radioactive northern blot method to detect small RNAs.
Kim SW, Li Z, Moore PS, Monaghan AP, Chang Y, Nichols M, John B.
Nucleic Acids Res. 2010 Apr;38(7):e98.

Sall genes regulate region-specific morphogenesis in the mouse limb by modulating Hox activities.
Kawakami Y, Uchiyama Y, Rodriguez Esteban C, Inenaga T, Koyano-Nakagawa N, Kawakami H, Marti M, Kmita M, Monaghan-Nichols P, Nishinakamura R, Izpisua Belmonte JC.
Development. 2009 Feb;136(4):585-94.

Sall3 is required for the terminal maturation of olfactory glomerular interneurons.
Harrison SJ, Parrish M, Monaghan AP.
J Comp Neurol. 2008 Apr 10;507(5):1780-94.

Sall1 regulates mitral cell development and olfactory nerve extension in the developing olfactory bulb.
Harrison SJ, Nishinakamura R, Monaghan AP.
Cereb Cortex. 2008 Jul;18(7):1604-17.

Abnormal development of zinc-containing cortical circuits in the absence of the transcription factor Tailless.
Land PW, Monaghan AP.
Brain Res Dev Brain Res. 2005 Aug 8;158(1-2):97-101.

PubMed Search for "Monaghan AP OR Monaghan-Nichols P"

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