The early isoform of disabled-1 functions independently of Reelin-mediated tyrosine phosphorylation in chick retina.
The Reelin-Disabled-1 (Dab1) signaling pathway plays a key role in the positioning of neurons during brain development. Two alternatively spliced Dab1 isoforms have been identified in chick retina and brain: Dab1-E, expressed at early stages of development, and Dab1-L (commonly referred to as Dab1), expressed at later developmental stages. The well-studied Dab1-L serves as an adaptor protein linking Reelin signal to its downstream effectors; however, nothing is known regarding the role of Dab1-E. Here we show that Dab1-E is primarily expressed in proliferating retinal progenitor cells whereas Dab1-L is found exclusively in differentiated neuronal cells. In contrast to Dab1-L, which is tyrosine phosphorylated upon Reelin stimulation, Dab1-E is not tyrosine phosphorylated and may function independently of Reelin. Knockdown of Dab1-E in chick retina results in a significant reduction in the number of proliferating cells and promotes ganglion cell differentiation. Our results demonstrate a role for Dab1-E in the maintenance of the retinal progenitor pool and determination of cell fate.
Gao
Zhihua
Z
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada.
Monckton
Elizabeth A
EA
Glubrecht
Darryl D
DD
Logan
Cairine
C
Godbout
Roseline
R
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000091042:Reelin Protein; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000166:cytology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology; D014443:Tyrosine / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D000091042:Reelin Protein; D014443:Tyrosine; D053829:Amyloid Precursor Protein Secretases; D012697:Serine Endopeptidases