An essential event in the development of the neural retina is the transition of proliferating progenitors to post- mitotic differentiated retinal neurons. Inhibition of this process alters the complement of cell types required for normal retinal organization and function. Proneural basic helix-loop-helix (bHLH) transcription factors play a central role in regulating the commitment of retinal progenitor cells to a differentiated retinal neuron fate. The Ath5 gene is required for the genesis of retinal ganglion cells (RGCs). The long-term goal of this proposal is to define the molecular pathway by which Ath5 regulates retinal neurogenesis. Ath5 expression is tightly coupled with the onset of retinal neurogenesis, and the timing of its expression is important for its ability to regulate RGC differentiation.
The first aim of the proposal will focus on characterizing the transcriptional regulatory mechanisms that provide spatial and temporal control of Ath5 expression. Next, to understand how Ath5 drives retinal differentiation it is important to investigate the function of genes that are regulated by Ath5 during retinal development. One of these Ath5 target genes, SBT1 (shared bHLH target 1), is a novel gene that functions as an essential effector for proneural bHLH factors in the developing retina. To understand the function of this novel gene, Aim 2 will focus on testing a predicted interaction between SBT1 and histone deactylase, while Aim 3 will be directed towards defining the molecular pathways that are dependent upon SBT1 during eye development. This work will advance our understanding of the mechanisms controlling retinal neuron differentiation, and will reveal the function of an important new gene in the proneural regulatory pathway, which could provide insight into developmental disorders affecting the retina. Ultimately, a detailed understanding of the factors determining retinal neuron fate in vivo will impact future efforts at replacing neurons lost to disease. Project Narrative An important goal of our research is to understand how cells in the retinal are generated during early eye development, since we may gain a better understanding of how these processes are disrupted in pathological situations, such as congenital disorders affecting vision. A long-term hope is that we may ultimately be able to manipulate the differentiation of retinal stem cells or progenitors to treat retinal degenerative diseases. Our work will contribute to this effort by characterizing the mechanisms underlying retinal neuron development.
|Willardsen, Minde; Hutcheson, David A; Moore, Kathryn B et al. (2014) The ETS transcription factor Etv1 mediates FGF signaling to initiate proneural gene expression during Xenopus laevis retinal development. Mech Dev 131:57-67|
|Aldiri, Issam; Moore, Kathryn B; Hutcheson, David A et al. (2013) Polycomb repressive complex PRC2 regulates Xenopus retina development downstream of Wnt/*-catenin signaling. Development 140:2867-78|
|Green, Yangsook Song; Vetter, Monica L (2011) EBF proteins participate in transcriptional regulation of Xenopus muscle development. Dev Biol 358:240-50|
|Green, Yangsook S; Vetter, Monica L (2011) EBF factors drive expression of multiple classes of target genes governing neuronal development. Neural Dev 6:19|
|Masserdotti, Giacomo; Badaloni, Aurora; Green, Yangsook Song et al. (2010) ZFP423 coordinates Notch and bone morphogenetic protein signaling, selectively up-regulating Hes5 gene expression. J Biol Chem 285:30814-24|
|Willardsen, Minde I; Suli, Arminda; Pan, Yi et al. (2009) Temporal regulation of Ath5 gene expression during eye development. Dev Biol 326:471-81|
|Aldiri, Issam; Vetter, Monica L (2009) Characterization of the expression pattern of the PRC2 core subunit Suz12 during embryonic development of Xenopus laevis. Dev Dyn 238:3185-92|
|Riesenberg, Amy N; Le, Tien T; Willardsen, Minde I et al. (2009) Pax6 regulation of Math5 during mouse retinal neurogenesis. Genesis 47:175-87|
|Logan, Mary A; Steele, Michael R; Vetter, Monica L (2005) Expression of synaptic vesicle two-related protein SVOP in the developing nervous system of Xenopus laevis. Dev Dyn 234:802-7|
|Logan, Mary A; Steele, Michael R; Van Raay, Terence J et al. (2005) Identification of shared transcriptional targets for the proneural bHLH factors Xath5 and XNeuroD. Dev Biol 285:570-83|
Showing the most recent 10 out of 22 publications