Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment

During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation

Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment

During T cell development, multipotent progenitors relinquish competence for other fates and commit to the T cell lineage by turning on Bcl11b, which encodes a transcription factor. To clarify lineage commitment mechanisms, we followed developing T cells at the single-cell level using Bcl11b knock-in fluorescent reporter mice. Notch signaling and Notch-activated transcription factors collaborate to activate Bcl11b expression irrespectively of Notch-dependent proliferation. These inputs work via three distinct, asynchronous mechanisms: an early locus 'poising' function dependent on TCF-1 and GATA-3, a stochastic-permissivity function dependent on Notch signaling, and a separate amplitude-control function dependent on Runx1, a factor already present in multipotent progenitors. Despite their necessity for Bcl11b expression, these inputs act in a stage-specific manner, providing a multitiered mechanism for developmental gene regulation

Use of GCL Measurement to Determine Prognosis in Distinct Types of Toxic Metabolic Optic Neuropathies

The Spectral Domain OCT (SD-OCT) provides diagnostic and prognostic value in toxic metabolic neuropathies. The purposes of this study are to determine patterns of macular ganglion cell layer (GCL) loss amongst alcohol-induced toxic metabolic, drug-induced toxic metabolic, and nutritional optic neuropathy and to determine how visual acuity loss correlates

A New Diagnostic Sign of Carotid-Cavernous Fistula: Delayed Retinal Venular Peak Blood Flow Velocity

Carotid-Cavernous Fistulas (CCF) may be difficult to diagnose without classic anterior ocular signs. We discovered a new specific retinal sign of CCF - delay in peak retinal venule flow relative to the adjacent arteriole that was not present in other forms of venous stasis. Our purpose was to elucidate new features of retinal blood flow specific for CCF

Complex Non-Tumor Retinal Ganglion Cell-Glial Interrelationships in Neurofibromatosis-Optic Pathway Glioma (NF1-OPG) Mice

We report further details of a mouse model for neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) formation that exhibits developmental abnormalities of retinal electrophysiology distinguishable from OPG formation per se. Underlying mechanisms may help explain variable visual loss among children with NF1 and OPGs and lead to improved diagnosis and treatment methods