Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth

Steven W. Wang, Xiuqian Mu, William J. Bowers, Dong Seob Kim, Daniel J. Plas, Michael C. Crair, Howard J. Federoff, Lin Gan, William H. Klein

Research output: Contribution to journalArticle

Abstract

In mice, Brn3 POU domain transcription factors play essential roles in the differentiation and survival of projection neurons within the retina, inner ear, dorsal root and trigeminal ganglia. During retinal ganglion cell differentiation, Brn3b is expressed first, followed by Brn3a and Brn3c. Targeted deletion of Brn3b, but not Brn3a or Brn3c, leads to a loss of most retinal ganglion cells before birth. However, as a few retinal ganglion cells are still present in Brn3b-/- mice, Brn3a and Brn3c may partially compensate for the loss of Brn3b. To examine the role of Brn3c in retinal ganglion cell development, we generated Brn3b/Brn3c double knockout mice and analyzed their retinas and optic chiasms. Retinal ganglion cell axons from double knockout mice were more severely affected than were those from Brn3b-deficient mice, indicating that Brn3c was required for retinal ganglion cell differentiation and could partially compensate for the loss of Brn3b. Moreover, Brn3c had functions in retinal ganglion cell differentiation separate from those of Brn3b. Ipsilateral and misrouted projections at the optic chiasm were overproduced in Brn3b-/- mice but missing were entirely in optic chiasms of Brn3b/Brn3c double knockout mice, suggesting that Brn3c controlled ipsilateral axon production. Forced expression of Brn3c in Brn3b-/- retinal explants restored neurite outgrowth, demonstrating that Brn3c could promote axon outgrowth in the absence of Brn3b. Our results reveal a complex genetic relationship between Brn3b and Brn3c in regulating the retinal ganglion cell axon outgrowth.

Original languageEnglish (US)
Pages (from-to)467-477
Number of pages11
JournalDevelopment
Volume129
Issue number2
StatePublished - Aug 20 2002
Externally publishedYes

Fingerprint

Retinal Ganglion Cells
Knockout Mice
Optic Chiasm
Cell Differentiation
Axons
Retina
POU Domain Factors
Trigeminal Ganglion
Neuronal Outgrowth
Spinal Ganglia
Inner Ear
Parturition
Neurons

Keywords

  • Axon outgrowth
  • Brn3
  • Mouse
  • Pathfinding
  • POU domain transcription factors
  • Retina
  • Retinal ganglion cell differentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Wang, S. W., Mu, X., Bowers, W. J., Kim, D. S., Plas, D. J., Crair, M. C., ... Klein, W. H. (2002). Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. Development, 129(2), 467-477.

Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. / Wang, Steven W.; Mu, Xiuqian; Bowers, William J.; Kim, Dong Seob; Plas, Daniel J.; Crair, Michael C.; Federoff, Howard J.; Gan, Lin; Klein, William H.

In: Development, Vol. 129, No. 2, 20.08.2002, p. 467-477.

Research output: Contribution to journalArticle

Wang, SW, Mu, X, Bowers, WJ, Kim, DS, Plas, DJ, Crair, MC, Federoff, HJ, Gan, L & Klein, WH 2002, 'Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth', Development, vol. 129, no. 2, pp. 467-477.
Wang SW, Mu X, Bowers WJ, Kim DS, Plas DJ, Crair MC et al. Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. Development. 2002 Aug 20;129(2):467-477.
Wang, Steven W. ; Mu, Xiuqian ; Bowers, William J. ; Kim, Dong Seob ; Plas, Daniel J. ; Crair, Michael C. ; Federoff, Howard J. ; Gan, Lin ; Klein, William H. / Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. In: Development. 2002 ; Vol. 129, No. 2. pp. 467-477.
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abstract = "In mice, Brn3 POU domain transcription factors play essential roles in the differentiation and survival of projection neurons within the retina, inner ear, dorsal root and trigeminal ganglia. During retinal ganglion cell differentiation, Brn3b is expressed first, followed by Brn3a and Brn3c. Targeted deletion of Brn3b, but not Brn3a or Brn3c, leads to a loss of most retinal ganglion cells before birth. However, as a few retinal ganglion cells are still present in Brn3b-/- mice, Brn3a and Brn3c may partially compensate for the loss of Brn3b. To examine the role of Brn3c in retinal ganglion cell development, we generated Brn3b/Brn3c double knockout mice and analyzed their retinas and optic chiasms. Retinal ganglion cell axons from double knockout mice were more severely affected than were those from Brn3b-deficient mice, indicating that Brn3c was required for retinal ganglion cell differentiation and could partially compensate for the loss of Brn3b. Moreover, Brn3c had functions in retinal ganglion cell differentiation separate from those of Brn3b. Ipsilateral and misrouted projections at the optic chiasm were overproduced in Brn3b-/- mice but missing were entirely in optic chiasms of Brn3b/Brn3c double knockout mice, suggesting that Brn3c controlled ipsilateral axon production. Forced expression of Brn3c in Brn3b-/- retinal explants restored neurite outgrowth, demonstrating that Brn3c could promote axon outgrowth in the absence of Brn3b. Our results reveal a complex genetic relationship between Brn3b and Brn3c in regulating the retinal ganglion cell axon outgrowth.",
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