Pleiotropic And Isoform-Specific Functions For Pitx2 In Superior Colliculus And Hypothalamic Neuronal Development, Mindy Waite
Dec 2012
Pleiotropic And Isoform-Specific Functions For Pitx2 In Superior Colliculus And Hypothalamic Neuronal Development, Mindy Waite
Mindy Waite
Transcriptional regulation of gene expression during development is critical for proper neuronal differentiation and migration. Alternative splicing and differential isoform expression have been demonstrated for most mammalian genes, but their specific contributions to gene function are not well understood. In mice, the transcription factor gene Pitx2 is expressed as three different isoforms (PITX2A, PITX2B, and PITX2C) which have unique amino termini and common DNA binding homeodomains and carboxyl termini. The specific roles of these isoforms in neuronal development are not known. Here we report the onset of Pitx2ab and Pitx2c isoform-specific expression by E9.5 in the developing mouse brain. Using …
Retinal Ganglion Cell Differentiation And Transplantation, Jonathan Hertz
Dec 2012
Retinal Ganglion Cell Differentiation And Transplantation, Jonathan Hertz
Jonathan Hertz
Adult central nervous system (CNS) neurons fail to regenerate following injury, and there is no repair or replacement of cells lost after injury or in neurodegenerative diseases. There is much interest in transplanting stem cell-derived neurons into the injured nervous system and enhancing the differentiation of donor cells into mature, integrated and functional neurons. Little is known, however, about what signals control the differentiation and integration of neurons, either during development or in the adult. Generating appropriate types of donor neurons from stem cells has been challenging because the signals that regulate neural subtype-specific fates are largely unknown. Therefore, it …
A Novel Taulacz Allele Reveals A Requirement For Pitx2 In Formation Of The Mammillothalamic Tract, Mindy Waite
Dec 2011
A Novel Taulacz Allele Reveals A Requirement For Pitx2 In Formation Of The Mammillothalamic Tract, Mindy Waite
Mindy Waite
The hypothalamic mammillary region is critical for spatial memory and vestibular processing. Pitx2 encodes a paired-like transcription factor that is highly expressed in the developing mammillary region and is required for subthalamic nucleus formation. Here we analyzed a loss of function Pitx2-TaulacZ knock-in allele to study the effects of Pitx2 deficiency on neuronal projections in the embryonic mammillary region. Pitx2-expressing neurons contribute axons to principal mammillary, mammillotegmental and mammillotectal tracts. Embryos with Pitx2 deficiency exhibit axonal fibers in the principal mammillary tract that are improperly bundled and disorganized, yet project caudally toward the tectum and tegmentum. Embryos …
Gabaergic And Glutamatergic Identities Of Developing Midbrain Pitx2 Neurons, Mindy Waite
Jan 2011
Gabaergic And Glutamatergic Identities Of Developing Midbrain Pitx2 Neurons, Mindy Waite
Mindy Waite
Pitx2, a paired-like homeodomain transcription factor, is expressed in post-mitotic neurons within highly restricted domains of the embryonic mouse brain. Previous reports identified critical roles for PITX2 in histogenesis of the hypothalamus and midbrain, but the cellular identities of PITX2-positive neurons in these regions were not fully explored. This study characterizes Pitx2 expression with respect to midbrain transcription factor and neurotransmitter phenotypes in mid-to-late mouse gestation. In the dorsal midbrain, we identified Pitx2-positive neurons in the stratum griseum intermedium (SGI) as GABAergic and observed a requirement for PITX2 in GABAergic differentiation. We also identified two Pitx2-positive neuronal populations in the …
