LIM-Homeodomain Transcription Factor LHX4 Is Required for the Differentiation of Retinal Rod Bipolar Cells and OFF-Cone Bipolar Subtypes.

Retinal bipolar cells (BCs) connect with photoreceptors and relay visual information to retinal ganglion cells (RGCs). Retina-specific deletion of Lhx4 in mice results in a visual defect resembling human congenital stationary night blindness. This visual dysfunction results from the absence of rod bipolar cells (RBCs) and the loss of selective rod-connecting cone bipolar cell (CBC) subtypes and AII amacrine cells (ACs). Inactivation of Lhx4 causes the apoptosis of BCs and cell fate switch from some BCs to ACs, whereas Lhx4 overexpression promotes BC genesis. Moreover, Lhx4 positively regulates Lhx3 expression to drive the fate choice of type 2 BCs over the GABAergic ACs. Lhx4 inactivation ablates Bhlhe23 expression, whereas overexpression of Bhlhe23 partially rescues RBC development in the absence of Lhx4. Thus, by acting upstream of Bhlhe23 , Prdm8 , Fezf2 , Lhx3 , and other BC genes, Lhx4 , together with Isl1 , could play essential roles in regulating the subtype-specific development of RBCs and CBCs. • Lhx4 null mice display a visual defect resembling human CSNB • Loss of Lhx4 results in the loss of rod bipolar cells (RBCs) and rod-connecting BCs • Lhx4 regulates cell fate choice of type 2 BCs over GABAergic amacrine cells through Lhx3 • Overexpression of Bhlhe23 partially rescues RBC development in the absence of Lhx4 Dong et al. show that the loss of Lhx4 in mice results in the loss of rod bipolar cells and rod-connecting bipolar cells and in a visual defect resembling human congenital stationary night blindness. Lhx4 , together with Isl1 , acts upstream of Bhlhe23 , Prdm8 , Fezf2 , and Lhx3 to regulate bipolar cell development. [ABSTRACT FROM AUTHOR]