The Transcription Factor Bhlhb4 Is Required for Rod Bipolar Cell Maturation

• Published in: Neuron (Cambridge, Mass.) Vol. 43; no. 6; pp. 779 - 793
• Main Authors: Bramblett, Debra E., Pennesi, Mark E., Wu, Samuel M., Tsai, Ming-Jer
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-09-2004; Elsevier Limited
• Subjects: Age Factors; Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors; beta-Galactosidase - metabolism; Blotting, Southern - methods; Calbindin 2; Calbindins; Calcium-Binding Proteins - metabolism; Caspase 3; Caspases - metabolism; Cell Count; Cells, Cultured; Cellular Senescence - physiology; Electroretinography - methods; Embryo, Mammalian; Evoked Potentials - genetics; Evoked Potentials - radiation effects; Eye Proteins; Fluorescent Antibody Technique - methods; Gene Expression - genetics; Gene Expression Regulation, Developmental; Genotype & phenotype; GTP-Binding Protein alpha Subunits, Gi-Go - metabolism; Homeodomain Proteins - metabolism; In Situ Hybridization; Indenes - metabolism; Membrane Glycoproteins - metabolism; Membrane Transport Proteins; Mice; Mice, Knockout; Microscopy, Electron - methods; Nerve Tissue Proteins - metabolism; Neurons; Neurons - physiology; Paired Box Transcription Factors; PAX6 Transcription Factor; Photic Stimulation - methods; Photoreceptors; Protein Kinase C - metabolism; Protein Kinase C-alpha; Repressor Proteins; Retina; Retina - cytology; Retina - embryology; Retina - ultrastructure; Retinal Rod Photoreceptor Cells - embryology; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - biosynthesis; S100 Calcium Binding Protein G - metabolism; S100 Proteins - metabolism; Stem Cells - physiology; Synapses - physiology; Synapses - ultrastructure; Transcription Factors - physiology; Transmission electron microscopy; Vesicular Glutamate Transport Protein 1; Vesicular Transport Proteins - metabolism
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2004.08.032

Retinal bipolar cells are essential to the transmission of light information. Although bipolar cell dysfunction can result in blindness, little is known about the factors required for bipolar cell development and functional maturation. The basic helix-loop-helix (bHLH) transcription factor
Bhlhb4 was found to be expressed in rod bipolar cells (RB). Electroretinograms (ERGs) in the adult
Bhlhb4 knockout (
Bhlhb4
−/−
) showed that the loss of
Bhlhb4 resulted in disrupted rod signaling and profound retinal dysfunction resembling human congenital stationary night blindness (CSNB), characterized by the loss of the scotopic ERG b-wave. A depletion of inner nuclear layer (INL) cells in the adult
Bhlhb4 knockout has been ascribed to the abolishment of the RB cell population during postnatal development. Other retinal cell populations including photoreceptors were unaltered. The timing of RB cell depletion in the
Bhlhb4
−/−
mouse suggests that
Bhlhb4 is essential for RB cell maturation.