Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina.
The mammalian retina comprises six major neuronal cell types and one glial type that are further classified into multiple subtypes based on their anatomical and functional differences. Nevertheless, how these subtypes arise remains largely unknown at the molecular level. Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic amacrine and Type 2 OFF-cone bipolar subtypes throughout retinogenesis. Targeted deletion of Bhlhb5 results in a significant reduction in the generation of these selective bipolar and amacrine subtypes. Furthermore, although a Bhlhb5-null mutation has no effect on the expression of bHLH-class retinogenic genes, Bhlhb5 expression overlaps with that of the pan-amacrine factor NeuroD and the expression of Bhlhb5 and NeuroD is negatively regulated by ganglion cell-competence factor Math5. Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes.
Feng
Liang
L
Center for Aging and Developmental Biology, University of Rochester, Rochester, NY 14642, USA.
Xie
Xiaoling
X
Joshi
Pushkar S
PS
Yang
Zhiyong
Z
Shibasaki
Koji
K
Chow
Robert L
RL
Gan
Lin
L
D025042:Amacrine Cells / Q000166:cytology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000166:cytology*; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D005680:gamma-Aminobutyric Acid; C117638:Atoh7 protein, mouse; C488357:Bhlhe22 protein, mouse; C093564:Neurogenic differentiation factor 1