Ldb1- and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in the retina

Jimmy de Melo, Brian S. Clark, Anand Venkataraman, Fion Shiau, Cristina Zibetti, Seth Blackshaw

Research output: Contribution to journalArticlepeer-review

Abstract

Precise control of the relative ratio of retinal neurons and glia generated during development is essential for visual function. We show that Lhx2, which encodes a LIM-homeodomain transcription factor essential for specification and differentiation of retinal Müller glia, also plays a crucial role in the development of retinal neurons. Overexpression of Lhx2 with its transcriptional co-activator Ldb1 triggers cell cycle exit and inhibits both Notch signaling and retinal gliogenesis. Lhx2/Ldb1 overexpression also induces the formation of wide-field amacrine cells (wfACs). In contrast, Rnf12, which encodes a negative regulator of LDB1, is necessary for the initiation of retinal gliogenesis. We also show that Lhx2-dependent neurogenesis and wfAC formation requires Ascl1 and Neurog2, and that Lhx2 is necessary for their expression, although overexpression of Lhx2/ Ldb1 does not elevate expression of these proneural bHLH factors. Finally, we demonstrate that the relative level of the LHX2-LDB1 complex in the retina decreases in tandem with the onset of gliogenesis. These findings show that control of Lhx2 function by Ldb1 and Rnf12 underpins the coordinated differentiation of neurons and Müller glia in postnatal retina.

Original languageEnglish (US)
Article numberdev159970
JournalDevelopment (Cambridge)
Volume145
Issue number9
DOIs
StatePublished - May 2018

Keywords

  • Cell fate
  • Co-factor
  • Gliogenesis
  • Neurogenesis
  • Retina
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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