Signaling and Gene Regulatory Networks in Mammalian Lens Development

Ales Cvekl, Xin Zhang

Research output: Contribution to journalReview article

44 Scopus citations

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)
Pages (from-to)677-702
Number of pages26
JournalTrends in Genetics
Volume33
Issue number10
DOIs
StatePublished - Oct 2017

Keywords

  • BMP
  • FGF
  • Pax6
  • Wnt signaling
  • cell determination
  • crystallins
  • differentiation
  • ectoderm
  • lens
  • pre-placodal region
  • retinoic acid

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Signaling and Gene Regulatory Networks in Mammalian Lens Development'. Together they form a unique fingerprint.

  • Cite this