Sip1 regulates the generation of the inner nuclear layer retinal cell lineages in mammals

Yotam Menuchin-Lasowski, Pazit Oren-Giladi, Qing Xie, Raaya Ezra-Elia, Ron Ofri, Shany Peled-Hajaj, Chen Farhy, Yujiro Higashi, Tom Van de Putte, Hisato Kondoh, Danny Huylebroeck, Ales Cvekl, Ruth Ashery-Padan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


The transcription factor Sip1 (Zeb2) plays multiple roles during CNS development from early acquisition of neural fate to cortical neurogenesis and gliogenesis. In humans, SIP1 (ZEB2) haploinsufficiency leads to Mowat–Wilson syndrome, a complex congenital anomaly including intellectual disability, epilepsy and Hirschsprung disease. Here we uncover the role of Sip1 in retinogenesis. Somatic deletion of Sip1 from mouse retinal progenitors primarily affects the generation of inner nuclear layer cell types, resulting in complete loss of horizontal cells and reduced numbers of amacrine and bipolar cells, while the number of Muller glia is increased. Molecular analysis places Sip1 downstream of the eye field transcription factor Pax6 and upstream of Ptf1a in the gene network required for generating the horizontal and amacrine lineages. Intriguingly, characterization of differentiation dynamics reveals that Sip1 has a role in promoting the timely differentiation of retinal interneurons, assuring generation of the proper number of the diverse neuronal and glial cell subtypes that constitute the functional retina in mammals.

Original languageAmerican English
Pages (from-to)2829-2841
Number of pages13
JournalDevelopment (Cambridge)
Issue number15
StatePublished - 1 Aug 2016

Bibliographical note

Publisher Copyright:
© 2016. Published by The Company of Biologists Ltd.


  • Differentiation
  • Neurogenesis
  • Progenitor
  • Retina
  • Retinogenesis
  • Sip1
  • Zeb2
  • Zfhx1b


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