Skip to main content

Sall1 Regulates Microglial Morphology Cell Autonomously in the Developing Retina

  • Conference paper
  • First Online:
Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1074))

Abstract

Retinal degeneration often accompanies microglial activation and infiltration of monocyte-derived macrophages into the retina, resulting in the coexistence of microglia and monocyte-derived macrophages in the retina. We previously showed that the Sall1 zinc-finger transcriptional factor is expressed specifically in microglia within the retinal phagocyte pool, and analyses of Sall1 knockout mice revealed that microglial morphology changed from a ramified to a more amoeboid appearance in the developing retina. To investigate further whether Sall1 functions autonomously in microglia, we generated Sall1 conditional knockout mice, in which Sall1 was depleted specifically in the Cx3cr1+ microglial compartment of the developing retina. Sall1-deficient microglia exhibited morphological abnormalities on embryonic day 18 that strikingly resembled the phenotype observed in Sall1 knockout mice, demonstrating that Sall1 regulates microglial morphology cell autonomously. Analysis of the postnatal retina revealed that Sall1-deficient microglia extended their processes and their morphology became comparable to that of wild-type microglia on postnatal day 21, indicating that Sall1 is essential for microglial ramification in the developing retina, but not in the postnatal retina.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82

    Article  CAS  PubMed  Google Scholar 

  • Goldmann T, Wieghofer P, Muller PF et al (2013) A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation. Nat Neurosci 16:1618–1626

    Article  CAS  PubMed  Google Scholar 

  • Kanda S, Tanigawa S, Ohmori T et al (2014) Sall1 maintains nephron progenitors and nascent nephrons by acting as both an activator and a repressor. J Am Soc Nephrol 25:2584–2595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawakami Y, Uchiyama Y, Rodriguez Esteban C et al (2009) Sall genes regulate region-specific morphogenesis in the mouse limb by modulating Hox activities. Development 136:585–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kierdorf K, Erny D, Goldmann T et al (2013) Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci 16:273–280

    Article  CAS  PubMed  Google Scholar 

  • Koso H, Tsuhako A, Lai CY et al (2016) Conditional rod photoreceptor ablation reveals Sall1 as a microglial marker and regulator of microglial morphology in the retina. Glia 64:2005–2024

    Article  PubMed  Google Scholar 

  • Matcovitch-Natan O, Winter DR, Giladi A et al (2016) Microglia development follows a stepwise program to regulate brain homeostasis. Science 353:aad8670

    Article  PubMed  Google Scholar 

  • Netzer C, Rieger L, Brero A et al (2001) SALL1, the gene mutated in Townes-Brocks syndrome, encodes a transcriptional repressor which interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. Hum Mol Genet 10:3017–3024

    Article  CAS  PubMed  Google Scholar 

  • Nishinakamura R, Matsumoto Y, Nakao K et al (2001) Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development 128:3105–3015

    CAS  PubMed  Google Scholar 

  • Parrish M, Ott T, Lance-Jones C et al (2004) Loss of the Sall3 gene leads to palate deficiency, abnormalities in cranial nerves, and perinatal lethality. Mol Cell Biol 24:7102–7012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prinz M, Priller J, Sisodia SS et al (2011) Heterogeneity of CNS myeloid cells and their roles in neurodegeneration. Nat Neurosci 14:1227–1235

    Article  CAS  PubMed  Google Scholar 

  • Sennlaub F, Auvynet C, Calippe B et al (2013) CCR2(+) monocytes infiltrate atrophic lesions in age-related macular disease and mediate photoreceptor degeneration in experimental subretinal inflammation in Cx3cr1 deficient mice. EMBO Mol Med 5:1775–1793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wake H, Moorhouse AJ, Jinno S et al (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29:3974–3980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yona S, Kim KW, Wolf Y et al (2013) Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 38:79–91

    Article  CAS  PubMed  Google Scholar 

  • Yuri S, Fujimura S, Nimura K et al (2009) Sall4 is essential for stabilization, but not for pluripotency, of embryonic stem cells by repressing aberrant trophectoderm gene expression. Stem Cells 27:796–805

    Article  CAS  PubMed  Google Scholar 

  • Zhao L, Zabel MK, Wang X et al (2015) Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration. EMBO Mol Med 7:1179–1197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank A. Tsuhako for technical assistance. This study was supported by the Japan Society for Promotion of Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sumiko Watanabe .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this paper

Check for updates. Verify currency and authenticity via CrossMark

Cite this paper

Koso, H., Nishinakamura, R., Watanabe, S. (2018). Sall1 Regulates Microglial Morphology Cell Autonomously in the Developing Retina. In: Ash, J., Anderson, R., LaVail, M., Bowes Rickman, C., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 1074. Springer, Cham. https://doi.org/10.1007/978-3-319-75402-4_26

Download citation

Publish with us

Policies and ethics