Abstract
Most regions of the vertebrate central nervous system develop by the sequential addition of different classes of neurons and glia. This phenomenon has been best characterized in laminated structures like the retina and the cerebral cortex, in which the progenitor cells in these structures are thought to change in their competence as development proceeds to generate different types of neurons in a stereotypic sequence that is conserved across vertebrates. We previously reported that conditional deletion of Dicer prevents the change in competence of progenitors to generate later-born cell types, suggesting that specific microRNAs (miRNAs) are required for this developmental transition. In this report, we now show that three miRNAs, let-7, miR-125, and miR-9, are key regulators of the early to late developmental transition in retinal progenitors: (i ) members of these three miRNA families increase over the relevant developmental period in normal retinal progenitors; (ii) inhibiting the function of these miRNAs produces changes in retinal development similar to Dicer CKO; (iii) overexpression of members of these three miRNA families in Dicer-CKO retinas can rescue the phenotype, allowing their progression to late progenitors; (iv) overexpression of these miRNAs can accelerate normal retinal development; (v) microarray and computational analyses of Dicer-CKO retinal cells identified two potential targets of the late-progenitor miRNAs: Protogenin (Prtg) and Lin28b; and (vi) overexpression of either Lin28 or Prtg can maintain the early progenitor state. Together, these data demonstrate that a conserved miRNA pathway controls a key step in the progression of temporal identity in retinal progenitors.
| Original language | English (US) |
|---|---|
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 110 |
| Issue number | 26 |
| DOIs | |
| State | Published - Jun 25 2013 |
| Externally published | Yes |
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Keywords
- Heterochronic
- Progenitor competence
ASJC Scopus subject areas
- General
Cite this
Conserved microRNA pathway regulates developmental timing of retinal neurogenesis. / La Torre Vila, Anna; Georgi, Sean; Reh, Thomas A.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 26, 25.06.2013.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Conserved microRNA pathway regulates developmental timing of retinal neurogenesis
AU - La Torre Vila, Anna
AU - Georgi, Sean
AU - Reh, Thomas A.
PY - 2013/6/25
Y1 - 2013/6/25
N2 - Most regions of the vertebrate central nervous system develop by the sequential addition of different classes of neurons and glia. This phenomenon has been best characterized in laminated structures like the retina and the cerebral cortex, in which the progenitor cells in these structures are thought to change in their competence as development proceeds to generate different types of neurons in a stereotypic sequence that is conserved across vertebrates. We previously reported that conditional deletion of Dicer prevents the change in competence of progenitors to generate later-born cell types, suggesting that specific microRNAs (miRNAs) are required for this developmental transition. In this report, we now show that three miRNAs, let-7, miR-125, and miR-9, are key regulators of the early to late developmental transition in retinal progenitors: (i ) members of these three miRNA families increase over the relevant developmental period in normal retinal progenitors; (ii) inhibiting the function of these miRNAs produces changes in retinal development similar to Dicer CKO; (iii) overexpression of members of these three miRNA families in Dicer-CKO retinas can rescue the phenotype, allowing their progression to late progenitors; (iv) overexpression of these miRNAs can accelerate normal retinal development; (v) microarray and computational analyses of Dicer-CKO retinal cells identified two potential targets of the late-progenitor miRNAs: Protogenin (Prtg) and Lin28b; and (vi) overexpression of either Lin28 or Prtg can maintain the early progenitor state. Together, these data demonstrate that a conserved miRNA pathway controls a key step in the progression of temporal identity in retinal progenitors.
AB - Most regions of the vertebrate central nervous system develop by the sequential addition of different classes of neurons and glia. This phenomenon has been best characterized in laminated structures like the retina and the cerebral cortex, in which the progenitor cells in these structures are thought to change in their competence as development proceeds to generate different types of neurons in a stereotypic sequence that is conserved across vertebrates. We previously reported that conditional deletion of Dicer prevents the change in competence of progenitors to generate later-born cell types, suggesting that specific microRNAs (miRNAs) are required for this developmental transition. In this report, we now show that three miRNAs, let-7, miR-125, and miR-9, are key regulators of the early to late developmental transition in retinal progenitors: (i ) members of these three miRNA families increase over the relevant developmental period in normal retinal progenitors; (ii) inhibiting the function of these miRNAs produces changes in retinal development similar to Dicer CKO; (iii) overexpression of members of these three miRNA families in Dicer-CKO retinas can rescue the phenotype, allowing their progression to late progenitors; (iv) overexpression of these miRNAs can accelerate normal retinal development; (v) microarray and computational analyses of Dicer-CKO retinal cells identified two potential targets of the late-progenitor miRNAs: Protogenin (Prtg) and Lin28b; and (vi) overexpression of either Lin28 or Prtg can maintain the early progenitor state. Together, these data demonstrate that a conserved miRNA pathway controls a key step in the progression of temporal identity in retinal progenitors.
KW - Heterochronic
KW - Progenitor competence
UR - http://www.scopus.com/inward/record.url?scp=84879509740&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879509740&partnerID=8YFLogxK
U2 - 10.1073/pnas.1301837110
DO - 10.1073/pnas.1301837110
M3 - Article
C2 - 23754433
AN - SCOPUS:84879509740
VL - 110
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 26
ER -