Expression of the homeodomain transcription factor Meis2 in the embryonic and postnatal retina.
Members of the Meis subfamily of homeodomain-containing transcription factors play important roles during development and disease. Here we report that the Meis family protein Meis2 is expressed by a subpopulation of gamma-aminobutyric acid (GABA)ergic amacrine (AM) cells in the adult and embryonic retina of different vertebrate species. In mice, Meis2-expressing (Meis2+) AM cells are not cholinergic or dopaminergic, but some are immunoreactive for neuronal nitric oxide synthase (bNOS). About 50% of the mouse Meis2+ AM cell population expresses the calcium-binding protein calretinin, and some Meis2+ AM cells show characteristics of Type II CD-15+ cells. AM cell expression of Meis2 is lost in a conditional knockout mouse model for Pax6, indicating a dependency upon Pax6. Bromodeoxyuridine pulse labeling experiments and immunohistochemical staining for the neuronal marker NeuN in embryonic mouse retinae indicate that Meis2 is an early marker for newly postmitotic AM cells. In addition, taking advantage of the protracted retinal development in humans, we show that newly generated AM cells express Meis2 before adopting the GABAergic or glycinergic neurotransmitter phenotype. As development proceeds, some AM cells lose Meis2 expression concomitantly with the appearance of glycine, while other AM cells retain Meis2 expression after they express GABA. These data identify Meis2 as a suitable marker for the study of AM cell diversity and development in addition to providing evidence for the stepwise specification of the glycinergic and GABAergic neurotransmitter phenotypes during AM cell differentiation.
Bumsted-O'Brien
Keely M
KM
Department of Neuroanatomy, Max-Planck-Institute for Brain Research, Deutschordenst. 46, 60218 Frankfurt, Germany.
Hendrickson
Anita
A
Haverkamp
Silke
S
Ashery-Padan
Ruth
R
Schulte
Dorothea
D
D025042:Amacrine Cells / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D004622:Embryo, Mammalian; D005136:Eye Proteins; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000172:deficiency; D051381:Rats; D012097:Repressor Proteins; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism*
D005136:Eye Proteins; D018398:Homeodomain Proteins; C102641:Mrg1 protein, mouse; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D052248:Nitric Oxide Synthase Type I; D001973:Bromodeoxyuridine