Mcrs1 is required for branchial arch and cranial cartilage development
Stephanie Keer1, Helene Cousin2, Karyn Jourdeuil1
1Department of Anatomy and Cell Biology, The George Washington University School of Medicine and Health Sciences, 2300 I (eye) Street, NW, Washington, DC, 20037, USA.
Developmental Biology
|June 13, 2022
Summary
Mcrs1 protein is crucial for craniofacial development, particularly inner ear and branchial arch formation. Its loss disrupts neural crest migration and cartilage development, causing defects linked to Branchio-otic/Branchio-oto-renal (BOR) syndrome.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Mcrs1 is a multifunctional protein impacting numerous cellular processes.
- Mcrs1 interacts with the Six1 transcription factor, modulating gene transcription.
- Mcrs1 loss-of-function affects neural plate, neural border, pre-placodal ectoderm, and neural crest genes.
Purpose of the Study:
- To investigate the role of Mcrs1 in the development of otic vesicles (OV) and branchial arches (BA).
- To determine if Mcrs1-mediated gene expression changes contribute to Branchio-otic/Branchio-oto-renal (BOR) syndrome phenotypes.
Main Methods:
- Mcrs1 knockdown experiments in embryonic models.
- Analysis of gene expression patterns in OV and BA.
- Assessment of cranial neural crest (NC) cell migration.
- Evaluation of craniofacial cartilage morphology.
Main Results:
- Mcrs1 is essential for OV gene expression related to inner ear formation, patterning, and otic capsule cartilage development.
- Mcrs1 knockdown altered gene expression in larval BA, with an expansion of emx2.
- Reduced Mcrs1 expression diminished tbx1 domains in BA1 and BA2.
- Impaired cranial NC migration and defects in lower jaw cartilages (infrarostral, Meckel's, ceratohyal) and otic capsule were observed.
Conclusions:
- Mcrs1 plays a significant role in craniofacial cartilage formation.
- Mcrs1 loss results in developmental defects consistent with reduced Six1 activity, aligning with BOR syndrome characteristics.
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