Ptf1a determines horizontal and amacrine cell fates during mouse retinal development.
The vertebrate neural retina comprises six classes of neurons and one class of glial cells, all derived from a population of multipotent progenitors. There is little information on the molecular mechanisms governing the specification of cell type identity from multipotent progenitors in the developing retina. We report that Ptf1a, a basic-helix-loop-helix (bHLH) transcription factor, is transiently expressed by post-mitotic precursors in the developing mouse retina. Recombination-based lineage tracing analysis in vivo revealed that Ptf1a expression marks retinal precursors with competence to exclusively produce horizontal and amacrine neurons. Inactivation of Ptf1a leads to a fate-switch in these precursors that causes them to adopt a ganglion cell fate. This mis-specification of neurons results in a complete loss of horizontal cells, a profound decrease of amacrine cells and an increase in ganglion cells. Furthermore, we identify Ptf1a as a primary downstream target for Foxn4, a forkhead transcription factor involved in the genesis of horizontal and amacrine neurons. These data, together with the previous findings on Foxn4, provide a model in which the Foxn4-Ptf1a pathway plays a central role in directing the differentiation of retinal progenitors towards horizontal and amacrine cell fates.
Fujitani
Yoshio
Y
Vanderbilt University Program in Developmental Biology and Department of Cell and Developmental Biology, Vanderbilt University Medical School, Nashville, TN 37232-8240, USA. yoshio-f@osb.att.ne.jp
Fujitani
Shuko
S
Luo
Huijun
H
Qiu
Feng
F
Burlison
Jared
J
Long
Qiaoming
Q
Kawaguchi
Yoshiya
Y
Edlund
Helena
H
MacDonald
Raymond J
RJ
Furukawa
Takahisa
T
Fujikado
Takashi
T
Magnuson
Mark A
MA
Xiang
Mengqing
M
Wright
Christopher V E
CV
D025042:Amacrine Cells / Q000196:embryology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D005136:Eye Proteins / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D051248:Retinal Horizontal Cells / Q000196:embryology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
D017931:DNA Primers; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; C438622:Foxn4 protein, mouse; D014157:Transcription Factors; C062602:transcription factor PTF1