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Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice
Author(s) -
Huang Liang,
Hu Fang,
Feng Liang,
Luo XiongJian,
Liang Guoqing,
Zeng XiangYun,
Yi JingLin,
Gan Lin
Publication year - 2014
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.24067
Subject(s) - biology , amacrine cell , gabaergic , microbiology and biotechnology , retina , cell fate determination , basic helix loop helix , neuroscience , genetics , transcription factor , inhibitory postsynaptic potential , gene , dna binding protein
Background: BHLHB5, an OLIG‐related basic helix‐loop‐helix transcription factor, is required for the development of a subset of gamma‐amino butyric acid–releasing (GABAergic) amacrine cells and OFF‐cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5's functional mechanism in retinogenesis, we used the Cre‐loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5 ‐null retinas. The Bhlhb5 ‐Cre knock‐in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5 ‐expressing cells, and the cell fates of Bhlhb5 ‐lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5 ‐null retinas. Results: In addition to GABAergic amacrine and OFF‐CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON‐bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF‐CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Conclusions: Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell‐autonomous as well as non‐cell‐autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes. Developmental Dynamics 243:279–289, 2014 . © 2013 Wiley Periodicals, Inc.