Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice

Liang Huang, Fang Hu, Liang Feng, Xiong Jian Luo, Guoqing Liang, Xiang Yun Zeng, Jing Lin Yi, Lin Gan

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalDevelopmental Dynamics
Volume243
Issue number2
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Fingerprint

Retinal Bipolar Cells
Amacrine Cells
Retina
Basic Helix-Loop-Helix Transcription Factors
Retinal Rod Photoreceptor Cells
Butyric Acid
Cell Lineage
Ganglia
Cholinergic Agents
Genetic Recombination

Keywords

  • Amacrine cell
  • Bhlhb5
  • Bipolar cell
  • Neurogenesis
  • Retina
  • Transcription factor

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Huang, L., Hu, F., Feng, L., Luo, X. J., Liang, G., Zeng, X. Y., ... Gan, L. (2014). Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice. Developmental Dynamics, 243(2), 279-289. https://doi.org/10.1002/dvdy.24067

Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice. / Huang, Liang; Hu, Fang; Feng, Liang; Luo, Xiong Jian; Liang, Guoqing; Zeng, Xiang Yun; Yi, Jing Lin; Gan, Lin.

In: Developmental Dynamics, Vol. 243, No. 2, 01.02.2014, p. 279-289.

Research output: Contribution to journalArticle

Huang, L, Hu, F, Feng, L, Luo, XJ, Liang, G, Zeng, XY, Yi, JL & Gan, L 2014, 'Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice', Developmental Dynamics, vol. 243, no. 2, pp. 279-289. https://doi.org/10.1002/dvdy.24067
Huang, Liang ; Hu, Fang ; Feng, Liang ; Luo, Xiong Jian ; Liang, Guoqing ; Zeng, Xiang Yun ; Yi, Jing Lin ; Gan, Lin. / Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice. In: Developmental Dynamics. 2014 ; Vol. 243, No. 2. pp. 279-289.
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AU - Hu, Fang

AU - Feng, Liang

AU - Luo, Xiong Jian

AU - Liang, Guoqing

AU - Zeng, Xiang Yun

AU - Yi, Jing Lin

AU - Gan, Lin

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AB - 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.

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KW - Neurogenesis

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