Control of neuronal morphology by the atypical cadherin Fat3

Neuron. 2011 Sep 8;71(5):820-32. doi: 10.1016/j.neuron.2011.06.026.


Neurons receive signals through dendrites that vary widely in number and organization, ranging from one primary dendrite to multiple complex dendritic trees. For example, retinal amacrine cells (ACs) project primary dendrites into a discrete synaptic layer called the inner plexiform layer (IPL) and only rarely extend processes into other retinal layers. Here, we show that the atypical cadherin Fat3 ensures that ACs develop this unipolar morphology. AC precursors are initially multipolar but lose neurites as they migrate through the neuroblastic layer. In fat3 mutants, pruning is unreliable and ACs elaborate two dendritic trees: one in the IPL and a second projecting away from the IPL that stratifies to form an additional synaptic layer. Since complex nervous systems are characterized by the addition of layers, these results demonstrate that mutations in a single gene can cause fundamental changes in circuit organization that may drive nervous system evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Video-Audio Media

MeSH terms

  • Age Factors
  • Amacrine Cells / classification
  • Amacrine Cells / cytology
  • Amacrine Cells / metabolism
  • Amacrine Cells / physiology*
  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cadherins / deficiency
  • Cadherins / physiology*
  • Cell Movement / genetics
  • Dendrites / genetics*
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Gene Expression Regulation, Developmental / genetics
  • Intercellular Signaling Peptides and Proteins
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron, Transmission / methods
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / physiology
  • RNA, Messenger / metabolism
  • Retina / cytology*
  • Retina / growth & development
  • Transcription Factors / genetics
  • Tyrosine 3-Monooxygenase / metabolism
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism


  • Atoh7 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Cadherins
  • Fat3 protein, mouse
  • Fjx1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Transcription Factors
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • transcription factor PTF1
  • Tyrosine 3-Monooxygenase