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In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

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Developmental Dynamics of Rett Syndrome.

Danielle Feldman¹, Abhishek Banerjee², Mriganka Sur¹

¹Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Neural Plasticity

|March 5, 2016

Summary

Rett Syndrome phenotypes appear early in brain development, not just postnatally. Understanding the timing of MeCP2 loss is crucial for developing effective treatments for this neurodevelopmental disorder.

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Area of Science:

Neuroscience
Developmental Biology
Genetics

Background:

Rett Syndrome was historically viewed as a postnatal developmental disorder.
Recent evidence indicates phenotypes manifest during early brain development, including neurogenesis and migration.

Purpose of the Study:

To highlight that Rett Syndrome phenotypes are present from the earliest stages of brain development.
To emphasize the role of MeCP2 in these early developmental processes.
To inform therapeutic strategies by considering the temporal dynamics of MeCP2 loss.

Main Methods:

Review of recent evidence on Rett Syndrome phenotypes.
Analysis of MeCP2 expression patterns during neuronal development.
Examination of the signaling, transcriptional, and epigenetic mechanisms affected by MeCP2.

Main Results:

Rett Syndrome phenotypes are evident during neurogenesis, migration, patterning, and synaptic development.
MeCP2, implicated in these phenotypes, is expressed early in neuronal progenitors and throughout adulthood.
MeCP2's effects are mediated through pleiotropic actions involving diverse molecular mechanisms.

Conclusions:

Rett Syndrome is a disorder with early-onset neurodevelopmental phenotypes.
The timing and developmental impact of MeCP2 loss are critical factors for therapeutic interventions.
Future treatments must account for the early and continuous role of MeCP2 in brain development.