MATH5 controls the acquisition of multiple retinal cell fates

Liang Feng, Zheng Hua Xie, Qian Ding, Xiaoling Xie, Richard T. Libby, Lin Gan

Research output: Contribution to journalArticle

Abstract

Math5-null mutation results in the loss of retinal ganglion cells (RGCs) and in a concurrent increase of amacrine and cone cells. However, it remains unclear whether there is a cell fate switch of Math5-lineage cells in the absence of Math5 and whether MATH5 cell-autonomously regulates the differentiation of the above retinal neurons. Here, we performed a lineage analysis of Math5-expressing cells in developing mouse retinas using a conditional GFP reporter (Z/EG) activated by a Math5-Cre knock-in allele. We show that during normal retinogenesis, Math5-lineage cells mostly develop into RGCs, horizontal cells, cone photoreceptors, rod photoreceptors, and amacrine cells. Interestingly, amacrine cells of Math5-lineage cells are predominately of GABAergic, cholinergic, and A2 subtypes, indicating that Math5 plays a role in amacrine subtype specification. In the absence of Math5, more Math5-lineage cells undergo cell fate conversion from RGCs to the above retinal cell subtypes, and occasionally to cone-bipolar cells and Müller cells. This change in cell fate choices is accompanied by an up-regulation of NEUROD1, RXR and BHLHB5, the transcription factors essential for the differentiation of retinal cells other than RGCs. Additionally, loss of Math5 causes the failure of early progenitors to exit cell cycle and leads to a significant increase of Math5-lineage cells remaining in cell cycle. Collectively, these data suggest that Math5 regulates the generation of multiple retinal cell types via different mechanisms during retinogenesis.

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Retinal Ganglion Cells
Amacrine Cells
Cell Cycle
Retinal Cone Photoreceptor Cells
Retinal Neurons
Retinal Rod Photoreceptor Cells
Cell Lineage
varespladib methyl
Cholinergic Agents
Retina
Cell Differentiation
Transcription Factors
Up-Regulation
Alleles
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

MATH5 controls the acquisition of multiple retinal cell fates. / Feng, Liang; Xie, Zheng Hua; Ding, Qian; Xie, Xiaoling; Libby, Richard T.; Gan, Lin.

In: Molecular brain, Vol. 3, No. 1, 36, 22.11.2010.

Research output: Contribution to journalArticle

Feng, L, Xie, ZH, Ding, Q, Xie, X, Libby, RT & Gan, L 2010, 'MATH5 controls the acquisition of multiple retinal cell fates', Molecular brain, vol. 3, no. 1, 36. https://doi.org/10.1186/1756-6606-3-36
Feng, Liang ; Xie, Zheng Hua ; Ding, Qian ; Xie, Xiaoling ; Libby, Richard T. ; Gan, Lin. / MATH5 controls the acquisition of multiple retinal cell fates. In: Molecular brain. 2010 ; Vol. 3, No. 1.

TY - JOUR

T1 - MATH5 controls the acquisition of multiple retinal cell fates

AU - Feng, Liang

AU - Xie, Zheng Hua

AU - Ding, Qian

AU - Xie, Xiaoling

AU - Libby, Richard T.

AU - Gan, Lin

PY - 2010/11/22

Y1 - 2010/11/22

N2 - Math5-null mutation results in the loss of retinal ganglion cells (RGCs) and in a concurrent increase of amacrine and cone cells. However, it remains unclear whether there is a cell fate switch of Math5-lineage cells in the absence of Math5 and whether MATH5 cell-autonomously regulates the differentiation of the above retinal neurons. Here, we performed a lineage analysis of Math5-expressing cells in developing mouse retinas using a conditional GFP reporter (Z/EG) activated by a Math5-Cre knock-in allele. We show that during normal retinogenesis, Math5-lineage cells mostly develop into RGCs, horizontal cells, cone photoreceptors, rod photoreceptors, and amacrine cells. Interestingly, amacrine cells of Math5-lineage cells are predominately of GABAergic, cholinergic, and A2 subtypes, indicating that Math5 plays a role in amacrine subtype specification. In the absence of Math5, more Math5-lineage cells undergo cell fate conversion from RGCs to the above retinal cell subtypes, and occasionally to cone-bipolar cells and Müller cells. This change in cell fate choices is accompanied by an up-regulation of NEUROD1, RXR and BHLHB5, the transcription factors essential for the differentiation of retinal cells other than RGCs. Additionally, loss of Math5 causes the failure of early progenitors to exit cell cycle and leads to a significant increase of Math5-lineage cells remaining in cell cycle. Collectively, these data suggest that Math5 regulates the generation of multiple retinal cell types via different mechanisms during retinogenesis.

AB - Math5-null mutation results in the loss of retinal ganglion cells (RGCs) and in a concurrent increase of amacrine and cone cells. However, it remains unclear whether there is a cell fate switch of Math5-lineage cells in the absence of Math5 and whether MATH5 cell-autonomously regulates the differentiation of the above retinal neurons. Here, we performed a lineage analysis of Math5-expressing cells in developing mouse retinas using a conditional GFP reporter (Z/EG) activated by a Math5-Cre knock-in allele. We show that during normal retinogenesis, Math5-lineage cells mostly develop into RGCs, horizontal cells, cone photoreceptors, rod photoreceptors, and amacrine cells. Interestingly, amacrine cells of Math5-lineage cells are predominately of GABAergic, cholinergic, and A2 subtypes, indicating that Math5 plays a role in amacrine subtype specification. In the absence of Math5, more Math5-lineage cells undergo cell fate conversion from RGCs to the above retinal cell subtypes, and occasionally to cone-bipolar cells and Müller cells. This change in cell fate choices is accompanied by an up-regulation of NEUROD1, RXR and BHLHB5, the transcription factors essential for the differentiation of retinal cells other than RGCs. Additionally, loss of Math5 causes the failure of early progenitors to exit cell cycle and leads to a significant increase of Math5-lineage cells remaining in cell cycle. Collectively, these data suggest that Math5 regulates the generation of multiple retinal cell types via different mechanisms during retinogenesis.

UR - http://www.scopus.com/inward/record.url?scp=78349276593&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78349276593&partnerID=8YFLogxK

U2 - 10.1186/1756-6606-3-36

DO - 10.1186/1756-6606-3-36

M3 - Article

C2 - 21087508

AN - SCOPUS:78349276593

VL - 3

JO - Molecular Brain

JF - Molecular Brain

SN - 1756-6606

IS - 1

M1 - 36

ER -