The T cell oncogene Tal2 is necessary for normal development of the mouse brain.
Transcription factors are commonly involved in leukemia by activation through chromosomal translocations and normally function in cell type(s) that differ from that of the tumor. TAL2 is a member of a basic helix-loop-helix gene family specifically involved in T cell leukemogenesis. Null mutations of Tal2 have been made in mice to determine its function during development. Tal2 null mutant mice show no obvious defects of hematopoiesis. During embryogenesis, Tal2 expression is restricted to the developing midbrain, dorsal diencephalon, and rostroventral diencephalic/telencephalic boundary, partly along presumptive developing fiber tracts. The null mutant mice are viable at birth but growth become progressively retarded and they do not survive to reproductive age. Tal2-deficient mice show a distinct dysgenesis of the midbrain tectum. Due to loss of superficial gray and optical layers, the superior colliculus is reduced in size and the inferior colliculus is abnormally rounded and protruding. Death is most likely due to progressive hydrocephalus which appears to be caused by obstruction of the foramen of Monro (the connection between the ventricles of the forebrain). Thus, in addition to its oncogenicity when ectopically expressed, Tal2 normally plays a pivotal role in brain development and without this gene, mice cannot survive to maturity.
Bucher
K
K
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, United Kingdom.
Sofroniew
M V
MV
Pannell
R
R
Impey
H
H
Smith
A J
AJ
Torres
E M
EM
Dunnett
S B
SB
Jin
Y
Y
Baer
R
R
Rabbitts
T H
TH
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D001921:Brain / Q000002:abnormalities / Q000196:embryology*; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D006410:Hematopoiesis / Q000235:genetics; D006849:Hydrocephalus / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D009857:Oncogenes; D014157:Transcription Factors / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C490129:Tal2 protein, mouse