Cellular expression of midkine-a and midkine-b during retinal development and photoreceptor regeneration in zebrafish.
In the retina of adult teleosts, stem cells are sustained in two specialized niches: the ciliary marginal zone (CMZ) and the microenvironment surrounding adult Müller glia. Recently, Müller glia were identified as the regenerative stem cells in the teleost retina. Secreted signaling molecules that regulate neuronal regeneration in the retina are largely unknown. In a microarray screen to discover such factors, we identified midkine-b (mdkb). Midkine is a highly conserved heparin-binding growth factor with numerous biological functions. The zebrafish genome encodes two distinct midkine genes: mdka and mdkb. Here we describe the cellular expression of mdka and mdkb during retinal development and the initial, proliferative phase of photoreceptor regeneration. The results show that in the embryonic and larval retina mdka and mdkb are expressed in stem cells, retinal progenitors, and neurons in distinct patterns that suggest different functions for the two molecules. Following the selective death of photoreceptors in the adult, mdka and mdkb are coexpressed in horizontal cells and proliferating Müller glia and their neurogenic progeny. These data reveal that Mdka and Mdkb are signaling factors present in the retinal stem cell niches in both embryonic and mature retinas, and that their cellular expression is actively modulated during retinal development and regeneration.
Calinescu
Anda-Alexandra
AA
Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48109, USA.
Vihtelic
Thomas S
TS
Hyde
David R
DR
Hitchcock
Peter F
PF
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D000078792:Midkine; D009416:Nerve Regeneration; D009457:Neuroglia / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D051248:Retinal Horizontal Cells / Q000378:metabolism; D055351:Retinal Neurons / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055153:Stem Cell Niche; D013234:Stem Cells / Q000378:metabolism*; D015027:Zebrafish
D016207:Cytokines; D012333:RNA, Messenger; D000078792:Midkine