Fat3 and Ena/VASP proteins influence the emergence of asymmetric cell morphology in the developing retina.
Neurons exhibit asymmetric morphologies throughout development - from migration to the elaboration of axons and dendrites - that are correctly oriented for the flow of information. For instance, retinal amacrine cells migrate towards the inner plexiform layer (IPL) and then retract their trailing processes, thereby acquiring a unipolar morphology with a single dendritic arbor restricted to the IPL. Here, we provide evidence that the Fat-like cadherin Fat3 acts during multiple stages of amacrine cell development in mice to orient overall changes in cell shape towards the IPL. Using a time-lapse imaging assay, we found that developing amacrine cells are less directed towards the IPL in the absence of Fat3, during both migration and retraction. Consistent with its predicted role as a cell-surface receptor, Fat3 functions cell-autonomously and is able to influence the cytoskeleton directly through its intracellular domain, which can bind and localize Ena/VASP family actin regulators. Indeed, a change in Ena/VASP protein distribution is sufficient to recapitulate the Fat3 mutant amacrine cell phenotype. Thus, Fat-like proteins might control the polarized development of tissues by sculpting the cytoskeleton of individual cells.
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Alexandra
A
Krol
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Steven J
SJ
Henle
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA Lisa_Goodrich@hms.harvard.edu.
Lisa V
0000-0002-3331-8600
LV
Goodrich
D000199:Actins / Q000378:metabolism; D025042:Amacrine Cells / Q000166:cytology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement; D016764:Cell Polarity; D048430:Cell Shape; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D016501:Neurites / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000196:embryology*
D000199:Actins; D015820:Cadherins; D004268:DNA-Binding Proteins; C092744:ENA-VASP proteins; C518412:Fat3 protein, mouse
Amacrine cell; Ena/VASP; Fat3; Planar polarity; Retinal development