The Journal of Neuroscience, January 30, 2008, 28(5):1109-1117; doi:10.1523/JNEUROSCI.4853-07.2008
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Cellular/Molecular
The Proneural Basic Helix-Loop-Helix Gene Ascl1a Is Required for Retina Regeneration
Blake V. Fausett,
Jessica D. Gumerson, and
Daniel Goldman
Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109
Correspondence should be addressed to Daniel Goldman, University of Michigan, 5045 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200. Email: neuroman{at}umich.edu
Unlike mammals, teleost fish can regenerate an injured retina, restoring lost visual function. Little is known of the molecular events that underlie retina regeneration. We previously found that in zebrafish, retinal injury stimulates Müller glia to generate multipotent
1-tubulin (
1T) and pax6-expressing progenitors for retinal repair. Here, we report the identification of a critical E-box in the
1T promoter that mediates transactivation by achaete-scute complex-like 1a (ascl1a) during retina regeneration. More importantly, we show that ascl1a is essential for retina regeneration. Within 4 h after retinal injury, ascl1a is induced in Müller glia. Knockdown of ascl1a blocks the induction of
1T and pax6 as well as Müller glial proliferation, consequently preventing the generation of retinal progenitors and their differentiated progeny. These data suggest ascl1a is required to convert quiescent Müller glia into actively dividing retinal progenitors, and that ascl1a is a key regulator in initiating retina regeneration.
Key words: ascl1a; Müller glia; stem cells; regeneration; retina; zebrafish
Received Oct. 25, 2007;
revised Dec. 3, 2007;
accepted Dec. 4, 2007.
Correspondence should be addressed to Daniel Goldman, University of Michigan, 5045 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200. Email: neuroman{at}umich.edu
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Z. Qin, L. K. Barthel, and P. A. Raymond
Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish
PNAS,
June 9, 2009;
106(23):
9310 - 9315.
[Abstract]
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