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Notch Signaling Pathway

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...

Notch Signaling Pathway

Notch Signaling Pathway

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

Regulation of Angiogenesis and Blood Supply

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...

Hedgehog Signaling Pathway

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

The Retinoblastoma Gene

The Retinoblastoma Gene

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Related Experiment Video

Updated: Mar 25, 2026

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis

Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis

Published on: December 12, 2019

Lhx2 Is an Essential Factor for Retinal Gliogenesis and Notch Signaling.

Jimmy de Melo¹, Cristina Zibetti¹, Brian S Clark¹

¹Solomon H. Snyder Department of Neuroscience.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience

|February 26, 2016

Summary

The LIM homeodomain transcription factor Lhx2 is essential for Müller glial (MG) development in the mouse retina. Lhx2 regulates MG specification and differentiation by controlling Notch pathway genes and gliogenic transcription factors.

Keywords:

Lhx2 Müller glia Notch differentiation retina

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Published on: September 19, 2025

Area of Science:

Neuroscience
Developmental Biology
Ophthalmology

Background:

Müller glia (MG) are crucial for retinal homeostasis and neuronal survival.
MG can act as stem cells for retinal regeneration in some vertebrates.
Mechanisms regulating MG development are unclear due to gene expression overlap.

Purpose of the Study:

To investigate the role of the LIM homeodomain transcription factor Lhx2 in Müller glial development.
To elucidate how Lhx2 regulates gliogenesis and differentiation in the retina.

Main Methods:

Temporally controlled conditional knock-out studies of Lhx2 in mouse retina.
Analysis of gene expression, including Notch pathway components and gliogenic transcription factors.
Investigation of Lhx2's role in Hes5-induced gliogenesis.

Main Results:

Lhx2 is required throughout all stages of MG development.
Lhx2 directly regulates Notch pathway genes (Notch1, Dll1, Dll3) and gliogenic factors (Hes1, Hes5, Sox8, Rax).
Lhx2 deficiency leads to downregulation of Notch pathway genes and loss of signaling.
Lhx2 is necessary for Hes5-mediated Müller gliogenesis.

Conclusions:

Lhx2 is a critical regulator of Müller glial development in the mouse retina.
Lhx2 acts in concert with the Notch pathway to drive MG specification and differentiation.
Understanding Lhx2's role provides insights into retinal development and regeneration.