Pushing the envelope of retinal ganglion cell genesis: context dependent function of Math5 (Atoh7).

Lev Prasov, Thomas M Glaser

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The basic-helix-loop helix factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) development. However, only 10% of Math5-expressing cells adopt the RGC fate, and most become photoreceptors. In principle, Math5 may actively bias progenitors towards RGC fate or passively confer competence to respond to instructive factors. To distinguish these mechanisms, we misexpressed Math5 in a wide population of precursors using a Crx BAC or 2.4 kb promoter, and followed cell fates with Cre recombinase. In mice, the Crx cone-rod homeobox gene and Math5 are expressed shortly after cell cycle exit, in temporally distinct, but overlapping populations of neurogenic cells that give rise to 85% and 3% of the adult retina, respectively. The Crx>Math5 transgenes did not stimulate RGC fate or alter the timing of RGC births. Likewise, retroviral Math5 overexpression in retinal explants did not bias progenitors towards the RGC fate or induce cell cycle exit. The Crx>Math5 transgene did reduce the abundance of early-born (E15.5) photoreceptors two-fold, suggesting a limited cell fate shift. Nonetheless, retinal histology was grossly normal, despite widespread persistent Math5 expression. In an RGC-deficient (Math5 knockout) environment, Crx>Math5 partially rescued RGC and optic nerve development, but the temporal envelope of RGC births was not extended. The number of early-born RGCs (before E13) remained very low, and this was correlated with axon pathfinding defects and cell death. Together, these results suggest that Math5 is not sufficient to stimulate RGC fate. Our findings highlight the robust homeostatic mechanisms, and role of pioneering neurons in RGC development.

Original languageEnglish (US)
Pages (from-to)214-230
Number of pages17
JournalDevelopmental Biology
Volume368
Issue number2
DOIs
StatePublished - Aug 15 2012

Fingerprint

Retinal Ganglion Cells
Transgenes
Cell Cycle
Parturition
Vertebrate Photoreceptor Cells
Homeobox Genes
Optic Nerve
Mental Competency
Population
Retina
Histology
Cell Death
Neurons

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Pushing the envelope of retinal ganglion cell genesis : context dependent function of Math5 (Atoh7). / Prasov, Lev; Glaser, Thomas M.

In: Developmental Biology, Vol. 368, No. 2, 15.08.2012, p. 214-230.

Research output: Contribution to journalArticle

@article{1d40573a01f44227a46dc399bda439e0,
title = "Pushing the envelope of retinal ganglion cell genesis: context dependent function of Math5 (Atoh7).",
abstract = "The basic-helix-loop helix factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) development. However, only 10{\%} of Math5-expressing cells adopt the RGC fate, and most become photoreceptors. In principle, Math5 may actively bias progenitors towards RGC fate or passively confer competence to respond to instructive factors. To distinguish these mechanisms, we misexpressed Math5 in a wide population of precursors using a Crx BAC or 2.4 kb promoter, and followed cell fates with Cre recombinase. In mice, the Crx cone-rod homeobox gene and Math5 are expressed shortly after cell cycle exit, in temporally distinct, but overlapping populations of neurogenic cells that give rise to 85{\%} and 3{\%} of the adult retina, respectively. The Crx>Math5 transgenes did not stimulate RGC fate or alter the timing of RGC births. Likewise, retroviral Math5 overexpression in retinal explants did not bias progenitors towards the RGC fate or induce cell cycle exit. The Crx>Math5 transgene did reduce the abundance of early-born (E15.5) photoreceptors two-fold, suggesting a limited cell fate shift. Nonetheless, retinal histology was grossly normal, despite widespread persistent Math5 expression. In an RGC-deficient (Math5 knockout) environment, Crx>Math5 partially rescued RGC and optic nerve development, but the temporal envelope of RGC births was not extended. The number of early-born RGCs (before E13) remained very low, and this was correlated with axon pathfinding defects and cell death. Together, these results suggest that Math5 is not sufficient to stimulate RGC fate. Our findings highlight the robust homeostatic mechanisms, and role of pioneering neurons in RGC development.",
author = "Lev Prasov and Glaser, {Thomas M}",
year = "2012",
month = "8",
day = "15",
doi = "10.1016/j.ydbio.2012.05.005",
language = "English (US)",
volume = "368",
pages = "214--230",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Pushing the envelope of retinal ganglion cell genesis

T2 - context dependent function of Math5 (Atoh7).

AU - Prasov, Lev

AU - Glaser, Thomas M

PY - 2012/8/15

Y1 - 2012/8/15

N2 - The basic-helix-loop helix factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) development. However, only 10% of Math5-expressing cells adopt the RGC fate, and most become photoreceptors. In principle, Math5 may actively bias progenitors towards RGC fate or passively confer competence to respond to instructive factors. To distinguish these mechanisms, we misexpressed Math5 in a wide population of precursors using a Crx BAC or 2.4 kb promoter, and followed cell fates with Cre recombinase. In mice, the Crx cone-rod homeobox gene and Math5 are expressed shortly after cell cycle exit, in temporally distinct, but overlapping populations of neurogenic cells that give rise to 85% and 3% of the adult retina, respectively. The Crx>Math5 transgenes did not stimulate RGC fate or alter the timing of RGC births. Likewise, retroviral Math5 overexpression in retinal explants did not bias progenitors towards the RGC fate or induce cell cycle exit. The Crx>Math5 transgene did reduce the abundance of early-born (E15.5) photoreceptors two-fold, suggesting a limited cell fate shift. Nonetheless, retinal histology was grossly normal, despite widespread persistent Math5 expression. In an RGC-deficient (Math5 knockout) environment, Crx>Math5 partially rescued RGC and optic nerve development, but the temporal envelope of RGC births was not extended. The number of early-born RGCs (before E13) remained very low, and this was correlated with axon pathfinding defects and cell death. Together, these results suggest that Math5 is not sufficient to stimulate RGC fate. Our findings highlight the robust homeostatic mechanisms, and role of pioneering neurons in RGC development.

AB - The basic-helix-loop helix factor Math5 (Atoh7) is required for retinal ganglion cell (RGC) development. However, only 10% of Math5-expressing cells adopt the RGC fate, and most become photoreceptors. In principle, Math5 may actively bias progenitors towards RGC fate or passively confer competence to respond to instructive factors. To distinguish these mechanisms, we misexpressed Math5 in a wide population of precursors using a Crx BAC or 2.4 kb promoter, and followed cell fates with Cre recombinase. In mice, the Crx cone-rod homeobox gene and Math5 are expressed shortly after cell cycle exit, in temporally distinct, but overlapping populations of neurogenic cells that give rise to 85% and 3% of the adult retina, respectively. The Crx>Math5 transgenes did not stimulate RGC fate or alter the timing of RGC births. Likewise, retroviral Math5 overexpression in retinal explants did not bias progenitors towards the RGC fate or induce cell cycle exit. The Crx>Math5 transgene did reduce the abundance of early-born (E15.5) photoreceptors two-fold, suggesting a limited cell fate shift. Nonetheless, retinal histology was grossly normal, despite widespread persistent Math5 expression. In an RGC-deficient (Math5 knockout) environment, Crx>Math5 partially rescued RGC and optic nerve development, but the temporal envelope of RGC births was not extended. The number of early-born RGCs (before E13) remained very low, and this was correlated with axon pathfinding defects and cell death. Together, these results suggest that Math5 is not sufficient to stimulate RGC fate. Our findings highlight the robust homeostatic mechanisms, and role of pioneering neurons in RGC development.

UR - http://www.scopus.com/inward/record.url?scp=84867909036&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867909036&partnerID=8YFLogxK

U2 - 10.1016/j.ydbio.2012.05.005

DO - 10.1016/j.ydbio.2012.05.005

M3 - Article

C2 - 22609278

AN - SCOPUS:84867909036

VL - 368

SP - 214

EP - 230

JO - Developmental Biology

JF - Developmental Biology

SN - 0012-1606

IS - 2

ER -