NeuroD induces the expression of visinin and calretinin by proliferating cells derived from toxin-damaged chicken retina.
Müller glia have been shown to be a potential source of neural regeneration in the avian retina. In response to acute damage Müller glia de-differentiate, proliferate, express transcription factors found in embryonic retinal progenitors, and some of the progeny differentiate into neurons and glia (Fischer and Reh [2001a] Nat. Neurosci. 4:247-252). However, most of the cells produced by proliferating Müller cells appear to remain undifferentiated. The purpose of this study was to test whether the neurogenic gene NeuroD can promote the differentiation of proliferating cells derived from the postnatal chick retina. We used recombinant avian retroviruses to transfect green fluorescent protein (GFP) or NeuroD. The majority of cells transfected with GFP remained undifferentiated, with a few cells differentiating into calretinin-immunoreactive neurons. Many cells transfected with the NeuroD-virus expressed calretinin, neurofilament, or visinin, while most cells remained undifferentiated. The number of calretinin-expressing cells that were generated was increased approximately 20-fold with forced expression of NeuroD. In addition, we found that cells transfected with NeuroD never expressed glutamine synthetase, a marker of mature Müller glia, suggesting that NeuroD suppresses glial differentiation. We conclude that NeuroD stimulates cells from the toxin-damaged chicken retina to acquire some neuronal phenotypes. We propose that most of these cells were derived from Müller glia.
Department of Neuroscience, Ohio State University, Columbus, Ohio, USA. fischer.412@osu.edu
Andy J
AJ
Fischer
Shu-Zhen
SZ
Wang
Thomas A
TA
Reh
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D064032:Calbindin 2; D002454:Cell Differentiation; D002455:Cell Division; D002642:Chick Embryo; D002645:Chickens; D018507:Gene Expression Regulation, Developmental; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D012160:Retina / Q000196:embryology*; D012190:Retroviridae / Q000235:genetics; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis*; D013997:Time Factors; D014118:Toxins, Biological / Q000378:metabolism; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D064032:Calbindin 2; D005974:Glutamate-Ammonia Ligase; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; D014118:Toxins, Biological; C045140:visinin; C093564:Neurogenic differentiation factor 1