BIO 138 GROUP 3 Prox1 down-regulation causes reduction of horizontal cells and failure of

Vertebrate Retinal Development: RPC to halt cell cycle

Neuroectoderm > eye primordia > optic vesicles > ciliary epithelia >
neural retina/RPC > retinal cell type
● these processes are controlled by basic-loop-helix (bHlH) genes or
homeobox genes
Homeobox genes in Retinal Development
These transcription factors act together for cell differentiation,
determination of retinal tissue which then leads to the development of the
three layers of retinal tissue namely , Ganglion Cell Layer (GLC), Inner
Nuclear Layer ( INL), Outer Nuclear Layer ( ONL).
Homeobox genes included in Pathway
● Rax- responsible for early development in eye and
photoreceptors
-upregulates Pax 6
- activates arrestin for determination of photocell receptor
● Pax 2 and Pax 6
Pax 2- retina
Pax 6- optic structures
No expression of Pax 2 results to failure of closing optic fissure.
-regulated by Fgfr1 and Fgfr2 (fibroblast growth factors )
● Vsx2 and Vsx1
-Vsx2 expressed in the interneurons of the retina, hindbrain and spinal
cord.
-Downregulation of the gene occurs when RPCs terminate cell cycle and
undergo differentiation.
-Vsx1 is primarily expressed in the postnatal retina
● Irx
-observed in the Glutamate-Cysteine Ligase (GCL) during early
retinal development. Required for the development of specific bipolar cell
subtypes
● Dlx
During development, there is a decrease in the proportion of
Dlx2 expressing genes in the total retinal population.
● Brn-3
The Brn-3 genes (BRN3a, BRN3b and BRN3c) are expressed specifically
in postmitotic RGCs in the embryonic and adult central nervous system
- required for the sensorineural development and survival

Pax 6- homolog of ey gene in Drosophila

Absence of Pax 6 leads to failure in activation of homeobox genes:
Atoh 7 and neurogenin 2 ( required for retinal neurogenesis and
development)

● Vax - for early neural development

Vax 1- found in basal forebrain,ventral optic vesicle and optic
disk
Absence of Vax1- defectuve RGC axonogenesis in mice
Vax 2- found in ventral optic vesicle.
Incorrect expression of Vax 2- alteration in dorsal and ventral
markers.
*Vax1 and Vax 2 downregulates Pax 6 expression

● Otx2- responsible for oral and nasal neural development.

-big role in photoreceptor cell determination
-greatly expressed in Retinal Pigment Epithelium
- weakly expressed in Neuroblastic Layer
Absence of the gene results to switching of the cell fate from
References
photoreceptors-->amacrine cells
Chen, J., Ma, L., Wang, S., Wang, X., Sun, Y., Gao, L. Li, J., & Zhou, G.
(2017). Analysis of expression of transcription factors in early human
● Crx- expressed in photoreceptors and pinealocytes (pineal
retina. International Journal of Developmental Neuroscience, 60, 94–102.
gland).
doi:10.1016/j.ijdevneu.2017.01.015
Lack of Crx gene expression causes failure in forming outer
photoreceptor segments.When regulated,Otx2 is repressed activating
photoreceptor genes. Kumar, J. P. (2001). Signalling pathways in Drosophila and vertebrate
retinal development. Nature Reviews Genetics, 2(11), 846–857.
● Oc1 and Oc2 doi:10.1038/35098564
Loss of Oc1 significantly affects horizontal cell genesis with an 80%
reduction in horizontal cells in the mature retina Zagozewski, J. L., Zhang, Q., Pinto, V. I., Wigle, J. T., & Eisenstat, D. D.
(2014). The role of homeobox genes in retinal development and disease.
● Lhx1 and Lhx2 Developmental Biology, 393(2), 195–208.
Lhx1 gene is observed in postmitotic horizontal cells.Reduction of Lhx1 doi:10.1016/j.ydbio.2014.07.004
expression causing the thinning of outer plexiform layer (layer that
contains the neural synapses in the retina).

Lhx2 is responsible for erythropoiesis, forebrain and eye development.

- Can act as an activator and repressor of transcription

Lhx2 down-regulation would cause large reduction to the amount of

Retinal Ganglion Cells (RGC).

● Prox1
-inducer of horizontal cell production and premature cell cycle inhibition.