TY - JOUR
T1 - BARHL2 differentially regulates the development of retinal amacrine and ganglion neurons
AU - Ding, Qian
AU - Chen, Hui
AU - Xie, Xiaoling
AU - Libby, Richard T.
AU - Tian, Ning
AU - Gan, Lin
PY - 2009/4/1
Y1 - 2009/4/1
N2 - Through transcriptional regulations, the BarH family of homeodomain proteins play essential roles in cell fate specification, cell differentiation, migration, and survival. Barhl2, a member of the Barh gene family, is expressed in retinal ganglion cells (RGCs), amacrine cells (ACs), and horizontal cells. Here, to investigate the role of Barhl2 in retinal development, Barhl2-deficient mice were generated. Analysis of AC subtypes in Barhl2-deficient retinas suggests that Barhl2 plays a critical role in AC subtype determination. A significant reduction of glycinergic and GABAergic ACs with a substantial increase in the number of cholinergic ACs was observed in Barhl2-null retinas. Barhl2 is also critical for the development of a normal complement of RGCs. Barhl2 deficiency resulted in a 35% increase in RGCs undergoing apoptosis during development. Genetic analysis revealed that Barhl2 functions downstream of the Atoh7-Pou4f3 regulatory pathway and regulates the maturation and/or survival of RGCs. Thus, BARHL2 appears to have numerous roles in retinal development, including regulating neuronal subtype specification, differentiation, and survival.
AB - Through transcriptional regulations, the BarH family of homeodomain proteins play essential roles in cell fate specification, cell differentiation, migration, and survival. Barhl2, a member of the Barh gene family, is expressed in retinal ganglion cells (RGCs), amacrine cells (ACs), and horizontal cells. Here, to investigate the role of Barhl2 in retinal development, Barhl2-deficient mice were generated. Analysis of AC subtypes in Barhl2-deficient retinas suggests that Barhl2 plays a critical role in AC subtype determination. A significant reduction of glycinergic and GABAergic ACs with a substantial increase in the number of cholinergic ACs was observed in Barhl2-null retinas. Barhl2 is also critical for the development of a normal complement of RGCs. Barhl2 deficiency resulted in a 35% increase in RGCs undergoing apoptosis during development. Genetic analysis revealed that Barhl2 functions downstream of the Atoh7-Pou4f3 regulatory pathway and regulates the maturation and/or survival of RGCs. Thus, BARHL2 appears to have numerous roles in retinal development, including regulating neuronal subtype specification, differentiation, and survival.
UR - http://www.scopus.com/inward/record.url?scp=65249183755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65249183755&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5237-08.2009
DO - 10.1523/JNEUROSCI.5237-08.2009
M3 - Article
C2 - 19339595
AN - SCOPUS:65249183755
SN - 0270-6474
VL - 29
SP - 3992
EP - 4003
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 13
ER -