N-myc regulates growth and fiber cell differentiation in lens development

Gabriel R. Cavalheiro, Gabriel E. Matos-Rodrigues, Yilin Zhao, Anielle L. Gomes, Deepti Anand, Danilo Predes, Silmara de Lima, Jose G. Abreu, Deyou Zheng, Salil A. Lachke, Ales Cvekl, Rodrigo A.P. Martins

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. We found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. Here, we examined the role of N-myc in mouse lens development. Genetic inactivation of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while “late” inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc-deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA-sequencing analysis of N-myc-deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens. Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage. Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis.

Original languageEnglish (US)
Pages (from-to)105-117
Number of pages13
JournalDevelopmental Biology
Volume429
Issue number1
DOIs
StatePublished - Sep 1 2017

Keywords

  • Cell cycle
  • Denucleation
  • Eye
  • Oncogene
  • Organogenesis
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'N-myc regulates growth and fiber cell differentiation in lens development'. Together they form a unique fingerprint.

  • Cite this

    Cavalheiro, G. R., Matos-Rodrigues, G. E., Zhao, Y., Gomes, A. L., Anand, D., Predes, D., de Lima, S., Abreu, J. G., Zheng, D., Lachke, S. A., Cvekl, A., & Martins, R. A. P. (2017). N-myc regulates growth and fiber cell differentiation in lens development. Developmental Biology, 429(1), 105-117. https://doi.org/10.1016/j.ydbio.2017.07.002