Abstract
Abstract: :
Purpose: To determine whether bipolar cell formation requires Chx10 and whether the developmental rescue that occurs in the Chx10,p27Kip1 double null (double–null) retina results in a restoration of visual circuitry and function. Methods: Cell composition analysis: Characteristic small molecular signatures of retinal cell populations from double–null and wildtype (wt) mice at ages ranging from postnatal day 8 (P8) to 4 weeks were acquired by Computational Molecular Phenotyping (CMP: Jones et al., J Comp Neurol, 2003). Visual Function and Circuitry: ERG recordings were performed on double–null and wt mice at ages ranging from P18 through 4 weeks. Results: CMP analysis revealed that the representatives major retinal cell classes, including cone bipolar cells, are present in the double–null retina. The exception is the rod bipolar cell population, which normally expresses Chx10: it is absent. Furthermore, there is evidence of retinal remodeling, including anomalous cell migration and neurite formation. ERG analysis showed a greatly diminished light response in the double–null mouse. Conclusions: A subset of cone bipolar cells do not require Chx10 for cell fate specification, whereas rod bipolar cells require Chx10 in a manner that is independent of the rescue due to p27Kip1 inactivation. Although p27Kip1 inactivation restores several features of retinal development that are compromised due to the loss of Chx10, the double–null mice still have profound defects in visual function. These findings suggest that Chx10 is necessary for many aspects of visual system development and that the anomalies still present in the double–null retina still attenuate visual function even though most cell classes are present.
Keywords: retinal development • retinal connections, networks, circuitry • bipolar cells