Signaling and Gene Regulatory Networks in Mammalian Lens Development

Ales Cvekl, Xin Zhang

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Ocular lens development represents an advantageous system in which to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and the underlying gene regulatory networks. Spatiotemporally regulated domains of BMP, FGF, and other signaling molecules in late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation. Extracellular signaling and DNA-binding transcription factors govern lens and optic cup morphogenesis. Pax6, c-Maf, Hsf4, Prox1, Sox1, and a few additional factors regulate the expression of the lens structural proteins, the crystallins. Extensive crosstalk between a diverse array of signaling pathways controls the complexity and order of lens morphogenetic processes and lens transparency. Recent progress based on RNA-seq and chromatin immunoprecipitation with deep sequencing (ChIP-seq) has provided novel insights into the chromatin and RNA expression landscape dynamics, and can be applied to studies of pre-placodal cells and their populations.Innovative technology can be used to visualize movements and cell fate decisions at the single-cell and single-molecule levels.Genome engineering using the CRISPR/Cas9 system accelerates studies of gene function, lncRNA functions, and distal enhancers.The nuclear organization changes dramatically during lens fiber cell differentiation as a result of the preparation of nuclei for their organized degradation.Development-controlling and congenital cataract-causing genes can be reliably predicted using the iSyTE database.

Original languageEnglish (US)
JournalTrends in Genetics
DOIs
StateAccepted/In press - 2017

Fingerprint

Gene Regulatory Networks
Lenses
Crystallins
Clustered Regularly Interspaced Short Palindromic Repeats
Long Noncoding RNA
RNA
Neural Plate
Gastrula
High-Throughput Nucleotide Sequencing
Crystalline Lens
Ectoderm
Chromatin Immunoprecipitation
Morphogenesis
Cataract
Genes
Chromatin
Cell Movement
Cell Differentiation
Transcription Factors
Stem Cells

Keywords

  • BMP
  • Cell determination
  • Crystallins
  • Differentiation
  • Ectoderm
  • FGF
  • Lens
  • Pax6
  • Pre-placodal region
  • Retinoic acid
  • Wnt signaling

ASJC Scopus subject areas

  • Genetics

Cite this

Signaling and Gene Regulatory Networks in Mammalian Lens Development. / Cvekl, Ales; Zhang, Xin.

In: Trends in Genetics, 2017.

Research output: Contribution to journalArticle

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