Characterization and function of the bHLH-O protein XHes2: insight into the mechanisms controlling retinal cell fate decision.
Neurons and glial cells differentiate from common multipotent precursors in the vertebrate retina. We have identified a novel member of the hairy/Enhancer of split [E(spl)] gene family in Xenopus, XHes2, as a regulator to bias retinal precursor cells towards a glial fate. XHes2 expression is predominantly restricted to sensory organ territories, including the retina. Using in vivo lipofection in the optic vesicle, we found that XHes2 overexpression dramatically increases gliogenesis at the expense of neurogenesis. This increase in glial cells correlates with a delayed cell cycle withdrawal of some retinal progenitors. In addition, birthdating experiments suggest that XHes2 deviates some early born cell types towards a glial fate that would normally have given rise to neurons. Conversely, a significant inhibition of glial differentiation is observed upon XHes2 loss of function. The gliogenic activity of XHes2 relies on its ability to inhibit neuronal differentiation by at least two distinct mechanisms: it not only negatively regulates XNgnr1 and NeuroD transcription, but it also physically interacts with a subset of proneural bHLH proteins.
Sölter
Marion
M
DFG-Center of Molecular Physiology of the Brain, Department of Developmental Biochemistry, University of Goettingen, Justus-von-Liebig-Weg 11, 37077 Goettingen, Germany.
Locker
Morgane
M
Boy
Sébastien
S
Taelman
Vincent
V
Bellefroid
Eric J
EJ
Perron
Muriel
M
Pieler
Tomas
T
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D047108:Embryonic Development / Q000235:genetics*; D005123:Eye / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D009475:Neurons, Afferent / Q000737:chemistry / Q000166:cytology; D051880:Receptors, Notch / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D029867:Xenopus Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D029867:Xenopus Proteins; C516060:Hes2 protein, Xenopus; C101907:neurogenin, Xenopus; C093564:Neurogenic differentiation factor 1