title: MATH5 controls the acquisition of multiple retinal cell fates.
abstract: Math5-null mutation results in the loss of retinal ganglion cells (RGCs) and in a concurrent increase of amacrine and cone cells. However, it remains unclear whether there is a cell fate switch of Math5-lineage cells in the absence of Math5 and whether MATH5 cell-autonomously regulates the differentiation of the above retinal neurons. Here, we performed a lineage analysis of Math5-expressing cells in developing mouse retinas using a conditional GFP reporter (Z/EG) activated by a Math5-Cre knock-in allele. We show that during normal retinogenesis, Math5-lineage cells mostly develop into RGCs, horizontal cells, cone photoreceptors, rod photoreceptors, and amacrine cells. Interestingly, amacrine cells of Math5-lineage cells are predominately of GABAergic, cholinergic, and A2 subtypes, indicating that Math5 plays a role in amacrine subtype specification. In the absence of Math5, more Math5-lineage cells undergo cell fate conversion from RGCs to the above retinal cell subtypes, and occasionally to cone-bipolar cells and Müller cells. This change in cell fate choices is accompanied by an up-regulation of NEUROD1, RXRγ and BHLHB5, the transcription factors essential for the differentiation of retinal cells other than RGCs. Additionally, loss of Math5 causes the failure of early progenitors to exit cell cycle and leads to a significant increase of Math5-lineage cells remaining in cell cycle. Collectively, these data suggest that Math5 regulates the generation of multiple retinal cell types via different mechanisms during retinogenesis.
authors.affiliation: Flaum Eye Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.forename: Zheng-hua
authors.initials: ZH
authors.lastname: Xie
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xie
authors.forename: Richard T
authors.initials: RT
authors.lastname: Libby
authors.forename: Lin
authors.initials: L
authors.lastname: Gan
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D049109:Cell Proliferation; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000196:embryology; D055351:Retinal Neurons / Q000166:cytology* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D009419:Nerve Tissue Proteins; C117638:Atoh7 protein, mouse