The Role of Math5 (Atoh7) in Retinal and Optic Nerve Development and Human Disease.

Retinal Development;ATOH7 (MATH5);Congenital Eye Disease;Optic Nerve;Cell Fate Determination;Retinal Ganglion Cell;Genetics;Health Sciences;Human Genetics

Prasov, LevRaymond, Pamela A. ;

University of Michigan

关键词: Retinal Development;    ATOH7 (MATH5);    Congenital Eye Disease;    Optic Nerve;    Cell Fate Determination;    Retinal Ganglion Cell;    Genetics;    Health Sciences;    Human Genetics;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/107270/lprasov_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Vertebrate retinal histogenesis is controlled by both intrinsic transcriptional programs and the microenvironment.The basic helix-loop-helix (bHLH) factor Math5 (Atoh7) is required for differentiation of retinal ganglion cells (RGC), which form the optic nerve.Math5 knockout mice lack RGCs, but only 10% of Math5-expressing progenitors adopt the RGC fate, and only 55% of RGCs are lineal descendents of Math5+ cells.To define the role of Math5 in RGC development, I characterized the transcriptional anatomy of mouse Math5, and showed that it is an unspliced, single-exon gene, contrary to a recent high-profile report.I then tested the contribution of Math5-expressing cells to the earliest born cohort of mouse retinal neurons, which consist primarily of RGCs (~80%). Unexpectedly, I found that only 20-30% of this cohort expresses Math5, yet most early RGCs depend on Math5 function, suggesting a non-autonomous role forMath5-expressing cells in RGC specification.Next, I evaluated the onset of Math5 expression, and that of RGC markers Brn3b and Isl1, with respect to the terminal cell cycle.Surprisingly, these markers were expressed by neurogenic cells prior to terminal mitosis during early development (H) in PHPV, and established causation, using biochemical and functional assays.Together, these studies provide important insights into the function of Math5 and RGC development.