Abstract
The basic helix-loop-helix (bHLH) transcription factor . Math5 (. Atoh7) is transiently expressed during early retinal histogenesis and is necessary for retinal ganglion cell (RGC) development. Using nucleoside pulse-chase experiments and clonal analysis, we determined that progenitor cells activate . Math5 during or after the terminal division, with progressively later onset as histogenesis proceeds. We have traced the lineage of . Math5+ cells using mouse BAC transgenes that express Cre recombinase under strict regulatory control. Quantitative analysis showed that . Math5+ progenitors express equivalent levels of . Math5 and contribute to every major cell type in the adult retina, but are heavily skewed toward early fates. The Math5. >. Cre transgene labels 3% of cells in adult retina, including 55% of RGCs. Only 11% of . Math5+ progenitors develop into RGCs; the majority become photoreceptors. The fate bias of the . Math5 cohort, inferred from the ratio of cone and rod births, changes over time, in parallel with the remaining neurogenic population. Comparable results were obtained using . Math5 mutant mice, except that ganglion cells were essentially absent, and late fates were overrepresented within the lineage. We identified . Math5-independent RGC precursors in the earliest born (embryonic day 11) retinal cohort, but these precursors require . Math5-expressing cells for differentiation. . Math5 thus acts permissively to establish RGC competence within a subset of progenitors, but is not sufficient for fate specification. It does not autonomously promote or suppress the determination of non-RGC fates. These data are consistent with progressive and temporal restriction models for retinal neurogenesis, in which environmental factors influence the final histotypic choice.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 395-413 |
| Number of pages | 19 |
| Journal | Developmental Biology |
| Volume | 365 |
| Issue number | 2 |
| DOIs | |
| State | Published - May 15 2012 |
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Keywords
- Atonal
- BAC transgenic
- BHLH
- Cell fate determination
- Cre recombinase
- Expression fate mapping
- Genetics
- Lineage
- Mouse
- Optic nerve
- Retina
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
- Molecular Biology
Cite this
Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle. / Brzezinski, Joseph A.; Prasov, Lev; Glaser, Thomas M.
In: Developmental Biology, Vol. 365, No. 2, 15.05.2012, p. 395-413.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Math5 defines the ganglion cell competence state in a subpopulation of retinal progenitor cells exiting the cell cycle
AU - Brzezinski, Joseph A.
AU - Prasov, Lev
AU - Glaser, Thomas M
PY - 2012/5/15
Y1 - 2012/5/15
N2 - The basic helix-loop-helix (bHLH) transcription factor . Math5 (. Atoh7) is transiently expressed during early retinal histogenesis and is necessary for retinal ganglion cell (RGC) development. Using nucleoside pulse-chase experiments and clonal analysis, we determined that progenitor cells activate . Math5 during or after the terminal division, with progressively later onset as histogenesis proceeds. We have traced the lineage of . Math5+ cells using mouse BAC transgenes that express Cre recombinase under strict regulatory control. Quantitative analysis showed that . Math5+ progenitors express equivalent levels of . Math5 and contribute to every major cell type in the adult retina, but are heavily skewed toward early fates. The Math5. >. Cre transgene labels 3% of cells in adult retina, including 55% of RGCs. Only 11% of . Math5+ progenitors develop into RGCs; the majority become photoreceptors. The fate bias of the . Math5 cohort, inferred from the ratio of cone and rod births, changes over time, in parallel with the remaining neurogenic population. Comparable results were obtained using . Math5 mutant mice, except that ganglion cells were essentially absent, and late fates were overrepresented within the lineage. We identified . Math5-independent RGC precursors in the earliest born (embryonic day 11) retinal cohort, but these precursors require . Math5-expressing cells for differentiation. . Math5 thus acts permissively to establish RGC competence within a subset of progenitors, but is not sufficient for fate specification. It does not autonomously promote or suppress the determination of non-RGC fates. These data are consistent with progressive and temporal restriction models for retinal neurogenesis, in which environmental factors influence the final histotypic choice.
AB - The basic helix-loop-helix (bHLH) transcription factor . Math5 (. Atoh7) is transiently expressed during early retinal histogenesis and is necessary for retinal ganglion cell (RGC) development. Using nucleoside pulse-chase experiments and clonal analysis, we determined that progenitor cells activate . Math5 during or after the terminal division, with progressively later onset as histogenesis proceeds. We have traced the lineage of . Math5+ cells using mouse BAC transgenes that express Cre recombinase under strict regulatory control. Quantitative analysis showed that . Math5+ progenitors express equivalent levels of . Math5 and contribute to every major cell type in the adult retina, but are heavily skewed toward early fates. The Math5. >. Cre transgene labels 3% of cells in adult retina, including 55% of RGCs. Only 11% of . Math5+ progenitors develop into RGCs; the majority become photoreceptors. The fate bias of the . Math5 cohort, inferred from the ratio of cone and rod births, changes over time, in parallel with the remaining neurogenic population. Comparable results were obtained using . Math5 mutant mice, except that ganglion cells were essentially absent, and late fates were overrepresented within the lineage. We identified . Math5-independent RGC precursors in the earliest born (embryonic day 11) retinal cohort, but these precursors require . Math5-expressing cells for differentiation. . Math5 thus acts permissively to establish RGC competence within a subset of progenitors, but is not sufficient for fate specification. It does not autonomously promote or suppress the determination of non-RGC fates. These data are consistent with progressive and temporal restriction models for retinal neurogenesis, in which environmental factors influence the final histotypic choice.
KW - Atonal
KW - BAC transgenic
KW - BHLH
KW - Cell fate determination
KW - Cre recombinase
KW - Expression fate mapping
KW - Genetics
KW - Lineage
KW - Mouse
KW - Optic nerve
KW - Retina
UR - http://www.scopus.com/inward/record.url?scp=84859941664&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859941664&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2012.03.006
DO - 10.1016/j.ydbio.2012.03.006
M3 - Article
VL - 365
SP - 395
EP - 413
JO - Developmental Biology
JF - Developmental Biology
SN - 0012-1606
IS - 2
ER -