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Differentiation

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Full-Text Articles in Developmental Neuroscience

Her9/Hes4 Is Required For Retinal Photoreceptor Development, Maintenance, And Survival, Cagney E. Coomer, Stephen G. Wilson, Kayla F. Titialii-Torres, Jessica D. Bills, Laura A. Krueger, Rebecca A. Petersen, Evelyn M. Turnbaugh, Eden L. Janesch, Ann C. Morris Jul 2020

Her9/Hes4 Is Required For Retinal Photoreceptor Development, Maintenance, And Survival, Cagney E. Coomer, Stephen G. Wilson, Kayla F. Titialii-Torres, Jessica D. Bills, Laura A. Krueger, Rebecca A. Petersen, Evelyn M. Turnbaugh, Eden L. Janesch, Ann C. Morris

Biology Faculty Publications

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased …

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Efficient In Vitro Development Of Photoreceptors From Human Pluripotent Stem Cells, Joseph C. Reynolds May 2015

Efficient In Vitro Development Of Photoreceptors From Human Pluripotent Stem Cells, Joseph C. Reynolds

Dissertations, Masters Theses, Capstones, and Culminating Projects

Degeneration of the rod and cone photoreceptors in the human retina is among the most common causes of blindness. Replacing these damaged photoreceptors may help to restore vision. Repairing the damaged retina relies on the insertion of new, healthy cells. Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are two possible sources of photoreceptors to restore vision. Previous data shows that human ES cells and iPS cells can be differentiated into photoreceptors and transplanted into the eye to restore some vision. However, this process is inefficient, and costly. Here, we show a new method for inducing photoreceptor production …

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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 …

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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 …

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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 …

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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 …

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