The Role of PTF1A in Spinal Cord Development

dc.contributor.advisorJohnson, Jane E.en
dc.creatorGlasgow, Stacey Marieen
dc.date.accessioned2010-07-12T18:53:39Z
dc.date.available2010-07-12T18:53:39Z
dc.date.issued2006-05-15
dc.description.abstractMutations in the human and mouse Ptf1a genes result in permanent diabetes mellitus and cerebellar agenesis. We show that PTF1a is present in precursors to GABAergic neurons in both the cerebellum and the spinal cord dorsal horn. A null mutation in Ptf1a reveals its requirement for the dorsal horn GABAergic neurons. Specifically, PTF1a is required for the generation of early born (dI4, E10.5) and late born (dILA, E12.5) dorsal interneuron populations identified by homeodomain factors Lhx1/5 and Pax2. Furthermore, in the absence of PTF1a, the dI4 dorsal interneurons trans-fate to dI5 (Lmx1b+), and the dILA to dILB (Lmx1b+;Tlx3+). This mis-specification of neurons results in a complete loss of inhibitory GABAergic neurons and an increase in the excitatory glutamatergic neurons in the dorsal horn of the spinal cord by E16.5. Thus, PTF1a function is an essential determinant for selecting the GABAergic over the glutamatergic neuronal cell fate in the developing spinal cord, and provides an important genetic link between inhibitory and excitatory interneuron development. Furthermore, Ptf1a appears to exert its functions within the neural tube, at least in part, as a component of a heterotrimeric complex composed of Ptf1a, E-protein, and Rbpsuh. Over-expression assays with Ptf1a and mutant forms of Ptf1a support a model in which the activity of Ptf1a is mediated by a balance between its participation in a trimeric complex, which includes Rbpsuh, and its participation as part of a heterodimer with E-proteins.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc70056531
dc.identifier.urihttps://hdl.handle.net/2152.5/711
dc.language.isoenen
dc.subjectDiabetes Mellitusen
dc.subjectGABAergic Neuronsen
dc.subjectTranscription Factorsen
dc.titleThe Role of PTF1A in Spinal Cord Developmenten
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2007-05-15
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineIntegrative Biologyen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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